• Users Online: 4072
  • Home
  • Print this page
  • Email this page
Export selected to
Endnote
Reference Manager
Procite
Medlars Format
RefWorks Format
BibTex Format
   Table of Contents - Current issue
Coverpage
February 2021
Volume 16 | Issue 2
Page Nos. 205-400

Online since Monday, August 24, 2020

Accessed 13,883 times.

PDF access policy
Journal allows immediate open access to content in HTML + PDF
View as eBookView issue as eBook
Access StatisticsIssue statistics
RSS FeedRSS
Hide all abstracts  Show selected abstracts  Export selected to  Add to my list
REVIEWS  

Role of apoptosis-inducing factor in perinatal hypoxic-ischemic brain injury Highly accessed article p. 205
Juan Rodriguez, Tao Li, Yiran Xu, Yanyan Sun, Changlian Zhu
DOI:10.4103/1673-5374.290875  PMID:32859765
Perinatal complications, such as asphyxia, can cause brain injuries that are often associated with subsequent neurological deficits, such as cerebral palsy or mental retardation. The mechanisms of perinatal brain injury are not fully understood, but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion. Among these proteins, apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia, but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury. In this review, we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy, specifically on the importance of apoptosis-inducing factor. The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality, especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress, acting as a free radical scavenger. We also discuss all the different apoptosis-inducing factor isoforms discovered, focusing especially on apoptosis-inducing factor 2, which is only expressed in the brain and the functions of which are starting now to be clarified. Finally, we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions (pro-survival and pro-apoptotic) and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Therapeutic potential of neuromodulation for demyelinating diseases Highly accessed article p. 214
Elliot H Choi, Chioma Nwakalor, Nolan J Brown, Joonho Lee, Michael Y Oh, In Hong Yang
DOI:10.4103/1673-5374.290876  PMID:32859766
Neuromodulation represents a cutting edge class of both invasive and non-invasive therapeutic methods which alter the activity of neurons. Currently, several different techniques have been developed - or are currently being investigated – to treat a wide variety of neurological and neuropsychiatric disorders. Recently, in vivo and in vitro studies have revealed that neuromodulation can also induce myelination, meaning that it could hold potential as a therapy for various demyelinating diseases including multiple sclerosis and progressive multifocal leukencepalopathy. These findings come on the heels of a paradigm shift in the view of myelin's role within the nervous system from a static structure to an active co-regulator of central nervous system plasticity and participant in neuron-mediated modulation. In the present review, we highlight several of the recent findings regarding the role of neural activity in altering myelination including several soluble and contact-dependent factors that seem to mediate neural activity-dependent myelination. We also highlight several considerations for neuromodulatory techniques, including the need for further research into spatiotemporal precision, dosage, and the safety and efficacy of transcranial focused ultrasound stimulation, an emerging neuromodulation technology. As the field of neuromodulation continues to evolve, it could potentially bring forth methods for the treatment of demyelinating diseases, and as such, further investigation into the mechanisms of neuron-dependent myelination as well as neuro-imaging modalities that can monitor myelination activity is warranted.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Dysfunctional glia: contributors to neurodegenerative disorders Highly accessed article p. 218
Marta Sidoryk-Wegrzynowicz, Lidia Strużyńska
DOI:10.4103/1673-5374.290877  PMID:32859767
Astrocytes are integral components of the central nervous system, where they are involved in numerous functions critical for neuronal development and functioning, including maintenance of blood-brain barrier, formation of synapses, supporting neurons with nutrients and trophic factors, and protecting them from injury. These roles are markedly affected in the course of chronic neurodegenerative disorders, often before the onset of the disease. In this review, we summarize the recent findings supporting the hypothesis that astrocytes play a fundamental role in the processes contributing to neurodegeneration. We focus on α-synucleinopathies and tauopathies as the most common neurodegenerative diseases. The mechanisms implicated in the development and progression of these disorders appear not to be exclusively neuronal, but are often related to the astrocytic-neuronal integrity and the response of astrocytes to the altered microglial function. A profound understanding of the multifaceted functions of astrocytes and identification of their communication pathways with neurons and microglia in health and in the disease is of critical significance for the development of novel mechanism-based therapies against neurodegenerative disorders.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Inflammation/bioenergetics-associated neurodegenerative pathologies and concomitant diseases: a role of mitochondria targeted catalase and xanthophylls Highly accessed article p. 223
Mikhail A Filippov, Olga G Tatarnikova, Natalia V Pozdnyakova, Vasily V Vorobyov
DOI:10.4103/1673-5374.290878  PMID:32859768
Various inflammatory stimuli are able to modify or even “re-program” the mitochondrial metabolism that results in generation of reactive oxygen species. In noncommunicable chronic diseases such as atherosclerosis and other cardiovascular pathologies, type 2 diabetes and metabolic syndrome, these modifications become systemic and are characterized by chronic inflammation and, in particular, “neuroinflammation” in the central nervous system. The processes associated with chronic inflammation are frequently grouped into “vicious circles” which are able to stimulate each other constantly amplifying the pathological events. These circles are evidently observed in Alzheimer's disease, atherosclerosis, type 2 diabetes, metabolic syndrome and, possibly, other associated pathologies. Furthermore, chronic inflammation in peripheral tissues is frequently concomitant to Alzheimer's disease. This is supposedly associated with some common genetic polymorphisms, for example, Apolipoprotein-E ε4 allele carriers with Alzheimer's disease can also develop atherosclerosis. Notably, in the transgenic mice expressing the recombinant mitochondria targeted catalase, that removes hydrogen peroxide from mitochondria, demonstrates the significant pathology amelioration and health improvements. In addition, the beneficial effects of some natural products from the xanthophyll family, astaxanthin and fucoxanthin, which are able to target the reactive oxygen species at cellular or mitochondrial membranes, have been demonstrated in both animal and human studies. We propose that the normalization of mitochondrial functions could play a key role in the treatment of neurodegenerative disorders and other noncommunicable diseases associated with chronic inflammation in ageing. Furthermore, some prospective drugs based on mitochondria targeted catalase or xanthophylls could be used as an effective treatment of these pathologies, especially at early stages of their development.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Potential therapeutic effects of polyphenols in Parkinson's disease: in vivo and in vitro pre-clinical studies p. 234
Claudio Giuliano, Silvia Cerri, Fabio Blandini
DOI:10.4103/1673-5374.290879  PMID:32859769
Parkinson's disease is a neurodegenerative disorder characterized by a combination of severe motor and non-motor symptoms. Over the years, several factors have been discovered to play a role in the pathogenesis of this disease, in particular, neuroinflammation and oxidative stress. To date, the pharmacological treatments used in Parkinson's disease are exclusively symptomatic. For this reason, in recent years, the research has been directed towards the discovery and study of new natural molecules to develop potential neuroprotective therapies against Parkinson's disease. In this context, natural polyphenols have raised much attention for their important anti-inflammatory and antioxidant properties, but also for their ability to modulate protein misfolding. In this review, we propose to summarize the relevant in vivo and in vitro studies concerning the potential therapeutic role of natural polyphenols in Parkinson's disease.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Possible implications of dysregulated nicotinic acetylcholine receptor diffusion and nanocluster formation in myasthenia gravis p. 242
Francisco J Barrantes
DOI:10.4103/1673-5374.290880  PMID:32859770
Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles. The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction, the nicotinic acetylcholine receptor. Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse. This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis. The review also covers the application of a powerful biophysical technique, superresolution optical microscopy, to image the nicotinic receptor in live cells and follow its motional dynamics. The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor, as observed in myasthenia gravis.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Hydrogel-based local drug delivery strategies for spinal cord repair p. 247
Robert B Shultz, Yinghui Zhong
DOI:10.4103/1673-5374.290882  PMID:32859771
Spinal cord injury results in significant loss of motor, sensory, and autonomic functions. Although a wide range of therapeutic agents have been shown to attenuate secondary injury or promote regeneration/repair in animal models of spinal cord injury, clinical translation of these strategies has been limited, in part due to difficulty in safely and effectively achieving therapeutic concentrations in the injured spinal cord tissue. Hydrogel-based drug delivery systems offer unique opportunities to locally deliver drugs to the injured spinal cord with sufficient dose and duration, while avoiding deleterious side effects associated with systemic drug administration. Such local drug delivery systems can be readily fabricated from biocompatible and biodegradable materials. In this review, hydrogel-based strategies for local drug delivery to the injured spinal cord are extensively reviewed, and recommendations are made for implementation.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Altered physiology of gastrointestinal vagal afferents following neurotrauma p. 254
Emily N Blanke, Gregory M Holmes, Emily M Besecker
DOI:10.4103/1673-5374.290883  PMID:32859772
The adaptability of the central nervous system has been revealed in several model systems. Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function. In both types of neurotrauma, traumatic brain injury and spinal cord injury, the primary parasympathetic control to the gastrointestinal tract, the vagus nerve, remains anatomically intact. However, individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions. Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury. While the vagal efferent output remains capable of eliciting motor responses following injury, evidence suggests impairment of the vagal afferents. Since sensory input drives motor output, this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Prospects for intelligent rehabilitation techniques to treat motor dysfunction p. 264
Cong-Cong Huo, Ya Zheng, Wei-Wei Lu, Teng-Yu Zhang, Dai-Fa Wang, Dong-Sheng Xu, Zeng-Yong Li
DOI:10.4103/1673-5374.290884  PMID:32859773
More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Microglia in neurodegenerative diseases p. 270
Yu Xu, Ming-Zhu Jin, Ze-Yong Yang, Wei-Lin Jin
DOI:10.4103/1673-5374.290881  PMID:32859774
A major feature of neurodegeneration is disruption of central nervous system homeostasis, during which microglia play diverse roles. In the central nervous system, microglia serve as the first line of immune defense and function in synapse pruning, injury repair, homeostasis maintenance, and regulation of brain development through scavenging and phagocytosis. Under pathological conditions or various stimulations, microglia proliferate, aggregate, and undergo a variety of changes in cell morphology, immunophenotype, and function. This review presents the features of microglia, especially their diversity and ability to change dynamically, and reinterprets their role as sensors for multiple stimulations and as effectors for brain aging and neurodegeneration. This review also summarizes some therapeutic approaches for neurodegenerative diseases that target microglia.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
PERSPECTIVES Top

Membrane progesterone receptors (mPRs/PAQRs) in Schwann cells represent a promising target for the promotion of neuroregeneration p. 281
Luca F Castelnovo, Peter Thomas, Valerio Magnaghi
DOI:10.4103/1673-5374.290885  PMID:32859775
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Nanoparticles as a tool to deliver drugs to the retina and brain: an update p. 283
Qing You, Bernhard A Sabel
DOI:10.4103/1673-5374.290886  PMID:32859776
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Stem cell heterogeneity and regenerative competence: the enormous potential of rare cells p. 285
Emily A.B. Gilbert, Cindi M Morshead
DOI:10.4103/1673-5374.290891  PMID:32859777
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Gut microbiota: a potential therapeutic target for Parkinson's disease p. 287
José Fidel Baizabal-Carvallo
DOI:10.4103/1673-5374.290896  PMID:32859778
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Novel Galectin-3 interactions involved in oligodendroglial differentiation make inroads into therapeutic strategies for demyelinating diseases p. 289
Laura Andrea Pasquini
DOI:10.4103/1673-5374.290887  PMID:32859779
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Oligodendrocytes in a dish for the drug discovery pipeline: the risk of oversimplification p. 291
Vito Antonio Baldassarro, Luciana Giardino, Laura Calzà
DOI:10.4103/1673-5374.290888  PMID:32859780
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

The role of NLRP3 inflammasome for microglial response to peripheral inflammation p. 294
Olga Garaschuk
DOI:10.4103/1673-5374.290889  PMID:32859781
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Multi-omics insights into neuronal regeneration and re-innervation p. 296
Muhammad Zain Chauhan, Sanjoy K Bhattacharya
DOI:10.4103/1673-5374.289434  PMID:32859782
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Chemical biology: a toolbox to unlock neurochemical epigenetics? p. 298
Dennis Ozcelik
DOI:10.4103/1673-5374.290890  PMID:32859783
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Excitotoxicity-induced endocytosis as a potential target for stroke neuroprotection p. 300
Margarita Diaz-Guerra
DOI:10.4103/1673-5374.290892  PMID:32859784
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Non-cell autonomous effect of neuronal nicotinamide phosphoribosyl transferase on the function of neuromuscular junctions p. 302
Samuel Lundt, Shinghua Ding
DOI:10.4103/1673-5374.290893  PMID:32859785
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Implications of Withaferin A in neurological disorders p. 304
Natasha Ram, Stephanie L Peak, Andres R Perez, Umesh K Jinwal
DOI:10.4103/1673-5374.290894  PMID:32859786
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

How does chronic dry eye shape peripheral and central nociceptive systems? p. 306
Adrian Guerrero-Moreno, Darine Fakih, Stéphane Melik Parsadaniantz, Annabelle Réaux-Le Goazigo
DOI:10.4103/1673-5374.290895  PMID:32859787
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Potential of kynurenine metabolites in drug development against neurodegenerative diseases p. 308
Lenka Kubicova, Vladimir Chobot
DOI:10.4103/1673-5374.290897  PMID:32859788
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Hypoxia in Alzheimer's disease: effects of hypoxia inducible factors p. 310
Halimatu Hassan, Ruoli Chen
DOI:10.4103/1673-5374.290898  PMID:32859789
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: BRAIN INJURY AND NEURAL REGENERATION Top

Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke p. 312
Jun Zhong, Rong-Wei Li, Ju Wang, Ying Wang, Hong-Fei Ge, Ji-Shu Xian, Hua Feng, Liang Tan
DOI:10.4103/1673-5374.290899  PMID:32859790
Cattle encephalon glycoside and ignotin (CEGI) injection is known as a multi-target neuroprotective drug that contains numerous liposoluble molecules, such as polypeptides, monosialotetrahexosyl ganglioside (GM-1), free amino acids, hypoxanthine and carnosine. CEGI has been approved by the Chinese State Food and Drug Administration and widely used in the treatments of various diseases, such as stroke and Alzheimer's disease. However, the neuroprotective effects of CEGI beyond the time window of thrombolysis (within 4.5 hours) on acute ischemic stroke remain unclear. This study constructed a rat middle cerebral artery occlusion model by suture-occluded method to simulate ischemic stroke. The first daily dose was intraperitoneally injected at 8 hours post-surgery and the CEGI treatments continued for 14 days. Results of the modified five-point Bederson scale, beam balance test and rotameric test showed the neurological function of ischemic stroke rats treated with 4 mL/kg/d CEGI improved significantly, but the mortality within 14 days did not change significantly. Brain MRI and 2,3,5-triphenyltetrazolium chloride staining confirmed that the infarct size in the 4 mL/kg/d CEGI-treated rats was significantly reduced compared with ischemic insult only. The results of transmission electron microscopy and double immunofluorescence staining showed that the hippocampal neuronal necrosis in the ischemic penumbra decreased whereas the immunopositivity of new neuronal-specific protein doublecortin and the percentage of Ki67/doublecortin positive cells increased in CEGI-treated rats compared with untreated rats. Our results suggest that CEGI has an effective neuroprotective effect on ischemic stroke when administered after the time window of thrombolysis. The study was approved by the Animal Ethics Committee of The Third Military Medical University, China.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Constraint-induced movement therapy enhances AMPA receptor-dependent synaptic plasticity in the ipsilateral hemisphere following ischemic stroke p. 319
Jian Hu, Pei-Le Liu, Yan Hua, Bei-Yao Gao, Yu-Yuan Wang, Yu-Long Bai, Chan Chen
DOI:10.4103/1673-5374.290900  PMID:32859791
Constraint-induced movement therapy (CIMT) can promote the recovery of motor function in injured upper limbs following stroke, which may be associated with upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) at synapses in the ipsilateral sensorimotor cortex in our previous study. However, AMPAR distribution is tightly regulated, and only AMPARs on the postsynaptic membrane can mediate synaptic transmission. We speculated that synaptic remodeling induced by movement-associated synaptic activity can promote functional recovery from stroke. To test this hypothesis, we compared AMPAR expression on the postsynaptic membrane surface in a rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) with versus without CIMT, which consisted of daily running wheel training for 2 weeks starting on day 7 after MCAO. The results showed that CIMT increased the number of glutamate receptor (GluR)2-containing functional synapses in the ipsilateral sensorimotor cortex, and reduced non-GluR2 AMPARs in the ipsilateral sensorimotor cortex and hippocampal CA3 region. In addition, CIMT enhanced AMPAR expression on the surface of post-synaptic membrane in the ipsilateral sensorimotor cortex and hippocampus. Thus, CIMT promotes the recovery of motor function of injured upper limbs following stroke by enhancing AMPAR-mediated synaptic transmission in the ischemic hemisphere. These findings provide supporting evidence for the clinical value of CIMT for restoring limb movement in stroke patients. All experimental procedures and protocols were approved by the Department of Laboratory Animal Science of Fudan University, China (approval No. 201802173S) on March 3, 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model p. 325
Zheng Zou, Yu-Shu Dong, Dong-Dong Liu, Gen Li, Guang-Zhi Hao, Xu Gao, Peng-Yu Pan, Guo-Biao Liang
DOI:10.4103/1673-5374.290904  PMID:32859792
Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is expressed in endothelial cells and activates inflammatory vascular damage. Endothelial cells are important components of the blood-brain barrier. To investigate whether MAP4K4 plays a role in the pathophysiology of subarachnoid hemorrhage, we evaluated the time-course expression of MAP4K4 after subarachnoid hemorrhage. A subarachnoid hemorrhage model was established using the intravascular perforation method. The model mice were assigned to four groups: MAP4K4 recombinant protein, scramble small interfering RNA, and MAP4K4 small interfering RNA were delivered by intracerebroventricular injection, while PF-06260933, a small-molecule inhibitor of MAP4K4, was administrated orally. Neurological score assessments, brain water assessments, Evans blue extravasation, immunofluorescence, western blot assay, and gelatin zymography were performed to analyze neurological outcomes and mechanisms of vascular damage. MAP4K4 expression was elevated in the cortex at 24 hours after subarachnoid hemorrhage, and colocalized with endothelial markers. MAP4K4 recombinant protein aggravated neurological impairment, brain edema, and blood-brain barrier damage; upregulated the expression of phosphorylated nuclear factor kappa B (p-p65) and matrix metalloproteinase 9 (MMP9); and degraded tight junction proteins (ZO-1 and claudin 5). Injection with MAP4K4 small interfering RNA reversed these effects. Furthermore, administration of the MAP4K4 inhibitor PF-06260933 reduced blood-brain barrier damage in mice, promoted the recovery of neurological function, and reduced p-p65 and MMP9 protein expression. Taken together, the results further illustrate that MAP4K4 causes early blood-brain barrier damage after subarachnoid hemorrhage. The mechanism can be confirmed by inhibiting the MAP4K4/NF-κB/MMP9 pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of General Hospital of Northern Theater Command (No. 2018002) on January 15, 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Identification of risk factors for poor language outcome in surgical resection of glioma involving the arcuate fasciculus: an observational study p. 333
Fang-Ye Li, Hong-Yu Liu, Jun Zhang, Zheng-Hui Sun, Jia-Shu Zhang, Guo-Chen Sun, Xin-Guang Yu, Xiao-Lei Chen, Bai-Nan Xu
DOI:10.4103/1673-5374.290901  PMID:32859793
The arcuate fasciculus is a critical component of the neural substrate of human language function. Surgical resection of glioma adjacent to the arcuate fasciculus likely damages this region. In this study, we evaluated the outcome of surgical resection of glioma adjacent to the arcuate fasciculus under the guidance of magnetic resonance imaging and diffusion tensor imaging, and we aimed to identify the risk factors for postoperative linguistic deficit. In total, 54 patients with primary glioma adjacent to the arcuate fasciculus were included in this observational study. These patients comprised 38 men and 16 women (aged 43 ± 11 years). All patients underwent surgical resenction of glioma under the guidance of magnetic resonance imaging and diffusion tensor imaging. Intraoperative images were updated when necessary for further resection. The gross total resection rate of the 54 patients increased from 38.9% to 70.4% by intraoperative magnetic resonance imaging. Preoperative language function and glioma-to-arcuate fasciculus distance were associated with poor language outcome. Multivariable logistic regression analyses showed that glioma-to-arcuate fasciculus distance was the major independent risk factor for poor outcome. The cutoff point of glioma-to-arcuate fasciculus distance for poor outcome was 3.2 mm. These findings suggest that intraoperative magnetic resonance imaging combined with diffusion tensor imaging of the arcuate fasciculus can help optimize tumor resection and result in the least damage to the arcuate fasciculus. Notably, glioma-to-arcuate fasciculus distance is a key independent risk factor for poor postoperative language outcome. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. S2014-096-01) on October 11, 2014.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Identification of predictive MRI and functional biomarkers in a pediatric piglet traumatic brain injury model p. 338
Hongzhi Wang, Emily W Baker, Abhyuday Mandal, Ramana M Pidaparti, Franklin D West, Holly A Kinder
DOI:10.4103/1673-5374.290915  PMID:32859794
Traumatic brain injury (TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments; however, identification of specific magnetic resonance imaging (MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee (AUP: A2015 11-001) on December 22, 2015.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation p. 345
Dong Chen, Jie Liu, Zhong Wu, Shao-Hua Li
DOI:10.4103/1673-5374.290908  PMID:32859795
Methyl-CpG-binding protein 2 (MeCP2) is a well-known transcription repressor, and mutations in MECP2 cause serious neurological disorders. Many studies have suggested that MeCP2 is involved in neural maturation only, and have not reported its role in neural stem cell differentiation. In the present study, we investigated this possible role of MeCP2 in neural stem cells. We used two different differentiation methods to explore how MeCP2 influences neural stem cell differentiation. When we transfected MeCP2-overexpressing lentivirus into neural stem cells, astrocytic differentiation was impaired. This impaired astrocytic differentiation occurred even in conditions of 20% fetal bovine serum, which favored astrocytic differentiation. In addition, miR-132 had the largest expression change after differentiation among several central nervous system related miRNAs. A luciferase assay confirmed that miR-132 directly targeted MeCP2, and that miR-132 was able to reduce MeCP2 expression at both the RNA and protein levels. The upregulation of miR-132 by miRNA mimics promoted astrocytic differentiation, which was fully recovered by MeCP2 overexpression. These results indicate that miR-132 regulates cell lineage differentiation by reducing MeCP2. The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital of TongJi University, China (approval No. SHDSYY-2018-4748) on March 10, 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: SPINAL CORD INJURY AND NEURAL REGENERATION Top

Total flavonoids of hawthorn leaves promote motor function recovery via inhibition of apoptosis after spinal cord injury p. 350
Qiong Zhang, Yin Xiong, Bo Li, Gui-Ying Deng, Wen-Wen Fu, Bai-Chuan Cao, Shao-Hui Zong, Gao-Feng Zeng
DOI:10.4103/1673-5374.286975  PMID:32859797
Flavonoids have been reported to have therapeutic potential for spinal cord injury. Hawthorn leaves have abundant content and species of total flavonoids, and studies of the effects of the total flavonoids of hawthorn leaves on spinal cord injury have not been published in or outside China. Therefore, Sprague-Dawley rats were used to establish a spinal cord injury model by Allen's method. Rats were intraperitoneally injected with 0.2 mL of different concentrations of total flavonoids of hawthorn leaves (5, 10, and 20 mg/kg) after spinal cord injury. Injections were administered once every 6 hours, three times a day, for 14 days. After treatment with various concentrations of total flavonoids of hawthorn leaves, the Basso, Beattie, and Bresnahan scores and histological staining indicated decreases in the lesion cavity and number of apoptotic cells of the injured spinal cord tissue; the morphological arrangement of the myelin sheath and nerve cells tended to be regular; and the Nissl bodies in neurons increased. The Basso, Beattie, and Bresnahan scores of treated spinal cord injury rats were increased. Western blot assays showed that the expression levels of pro-apoptotic Bax and cleaved caspase-3 were decreased, but the expression level of the anti-apoptotic Bcl-2 protein was increased. The improvement of the above physiological indicators showed a dose-dependent relationship with the concentration of total flavonoids of hawthorn leaves. The above findings confirm that total flavonoids of hawthorn leaves can reduce apoptosis and exert neuroprotective effects to promote the recovery of the motor function of rats with spinal cord injury. This study was approved by the Ethics Committee of the Guangxi Medical University of China (approval No. 201810042) in October 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury p. 357
Rustem R Islamov, Farid V Bashirov, Mikhail E Sokolov, Andrei A Izmailov, Filip O Fadeev, Vage A Markosyan, Maria A Davleeva, Olga V Zubkova, Maxim M Smarov, Denis Yu Logunov, Boris S Naroditskyi, Ilnur I Salafutdinov, Albert A Rizvanov, Ramil G Turaev
DOI:10.4103/1673-5374.290902  PMID:32859798
We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases, neurotrauma, and stroke. In this study, using a mini pig model of spinal cord injury, we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy. Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector (Ad5/35F) that carried an enhanced green fluorescent protein (EGFP) reporter gene in the plastic blood bag. The day after blood donation, the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate. A week after gene-modified leucoconcentrate therapy, fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury. In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed. In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes. Thus, the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions. This paper presents a proof-of-concept of simple, safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 5) on May 27, 2014.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series p. 362
Joseph A Shehadi, Steven M Elzein, Paul Beery, M Chance Spalding, Michelle Pershing
DOI:10.4103/1673-5374.290903  PMID:32859799
Administration of platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) has shown some promise in the treatment of neurological conditions; however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury (SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index (ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high (> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28–40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the OhioHealth Institutional Review Board (IRB No. 1204946) on May 16, 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: OPTIC NERVE INJURY AND NEURAL REGENERATION Top

Inhibition of GABAA-ρ receptors induces retina regeneration in zebrafish p. 367
Matthew R Kent, Nergis Kara, James G Patton
DOI:10.4103/1673-5374.286972  PMID:32859800
A potential treatment for retinal diseases is to induce an endogenous Müller glia (MG)-derived regenerative response to replace damaged neurons. In contrast to mammalian MG, zebrafish MG are capable of mediating spontaneous regeneration. We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration. We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A (GABAA) receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration, as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells. Here, we show that inhibition of a pharmacologically distinct subset of GABAA receptors (GABAA-ρ) can also induce retina regeneration. Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration. Gene expression analyses indicate that inhibition of GABAA-ρ receptors induces a canonical retinal regenerative response. Our results support a model in which decreased levels of GABA, such as would occur after retinal cell death or damage, induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration. Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee (Protocol M1800200) on January 29, 2019.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: SPINAL CORD INJURY AND NEURAL REGENERATION Top

Effectiveness of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury: a randomized controlled trial p. 375
Xiao-Ying Zhang, Yi-Chuan Song, Chang-Bin Liu, Chuan Qin, Song-Huai Liu, Jian-Jun Li
DOI:10.4103/1673-5374.290909  PMID:32859801
Singing, as a method of combining respiratory function exercise and vocal intonation therapy, provides a new direction for respiratory function exercise in patients with spinal cord injury. This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury. Among 31 included patients with spinal cord injury, 18 completed the treatment. These 18 patients were randomly assigned to undergo music therapy (intervention group, 30 min/d, 5 times a week, for a total of 12 weeks; n = 9, 7 males and 2 females; 30.33 ± 11.74 years old) or normal respiratory training (control group, n = 9; 8 males and 1 female; 34.78 ± 11.13 years old). Both patient groups received routine treatment concurrently. Before and at 6 and 12 weeks after intervention, a standard respiratory function test, a voice test, the St. George's Respiratory Questionnaire, and a quality of life questionnaire were administered. The results showed that the inspiratory capacity, forced expiratory volume in 1 second, forced vital capacity, maximal mid-expiratory flow rate, sing-loud pressure level, and sustained note length were significantly increased in the intervention group compared with the control group. The St. George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group. These findings suggest that oral motor respiratory exercise and vocal intonation therapy, as respiratory training methods in music therapy, are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2019-78-1) on May 27, 2019 and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1900026922) on October 26, 2019.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Dynamic changes in the systemic immune responses of spinal cord injury model mice p. 382
Tian-Yun Gao, Fei-Fei Huang, Yuan-Yuan Xie, Wen-Qing Wang, Liu-Di Wang, Dan Mu, Yi Cui, Bin Wang
DOI:10.4103/1673-5374.290910  PMID:32859802
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: PERIPHERAL NERVE INJURY AND NEURAL REGENERATION Top

Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging p. 388
Xiang-Xin Xing, Mou-Xiong Zheng, Xu-Yun Hua, Shu-Jie Ma, Zhen-Zhen Ma, Jian-Guang Xu
DOI:10.4103/1673-5374.290912  PMID:32859803
Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity. However, the underlying mechanism remains unclear. We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis. The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument (0.45 N, 120 times/min, 10 minutes daily, for 4 successive weeks). Resting-state functional magnetic resonance imaging revealed that compared with control rats, the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection. However, amplitudes were significantly higher in the massage group than in a sham-massage group. These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair. This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China (approval No. 201701001) on January 12, 2017.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
RESEARCH ARTICLES: OPTIC NERVE INJURY AND NEURAL REGENERATION Top

Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons p. 394
Jing Zhang, Zhi-Peng Lai, Pei Chen, Yang Ying, Jing Zhuang, Ke-Ming Yu
DOI:10.4103/1673-5374.290913  PMID:32859805
Glycogen synthase kinase-3β (GSK-3β) has been shown to attenuate DNA damage in nerve cells, thereby enhancing neuronal survival under pathological conditions; however, the underlying mechanism remains unclear. An in vitro serum-starvation retinal neuron model and in vivo ischemia/reperfusion retina injury rat model were established and treated with SB216763, a GSK-3β inhibitor. SB21673 decreased the formation of γ-H2A histone family member X foci and enhanced the viability of ischemic retinal neurons. In addition, SB216763 upregulated expression of phosphorylated-CREB1, a ligase IV transcription factor, and significantly increased the transcriptional activity of ligase IV in ischemic retinal neurons. These results were confirmed in rat retinas following ischemia/reperfusion injury. Furthermore, we found that unlike lithium chlorine (a well-known direct inhibitor of GSK-3β), SB216763 inhibited GSK-3β activity by suppressing its phosphorylation. Taken together, our results suggest that GSK-3β inhibition enhances repair of DNA double-strand breaks by upregulating ligase IV expression in ischemic retinal neurons. This study was approved by the Institutional Animal Care and Use Committee of Zhongshan Ophthalmic Center on February 18, 2018.
[ABSTRACT]  [HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
CORRIGENDA Top

Corrigendum: Delayed peripheral nerve repair: methods, including surgical ‘cross-bridging’ to promote nerve regeneration  

DOI:10.4103/1673-5374.290906  PMID:32859796
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta

Corrigendum: Sciatic nerve injury alters the spatial arrangement of neurons and glial cells in the anterior horn of the spinal cord  

DOI:10.4103/1673-5374.290907  PMID:32859804
[HTML Full text]  [PDF]  [Mobile Full text]  [EPub]  [PubMed]  [Sword Plugin for Repository]Beta
Feedback
Subscribe

Subscribe this journal
Submit articles
Most popular articles
Join us as a reviewer
Most Cited Articles
Email alerts
Recommend this journal