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Function of microglia and macrophages in secondary damage after spinal cord injury
Xiang Zhou, Xijing He, Yi Ren
15th October 2014, 9(20):1787-1795
Spinal cord injury (SCI) is a devastating type of neurological trauma with limited therapeutic opportunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contributor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of microglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.
  64 4,450 943
Autophagy: a double-edged sword for neuronal survival after cerebral ischemia
Wenqi Chen, Yinyi Sun, Kangyong Liu, Xiaojiang Sun
15th June 2014, 9(12):1210-1216
DOI:10.4103/1673-5374.135329  PMID:25206784
Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether activation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.
  64 4,504 1,105
Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease
Madhuri Venigalla, Sandra Sonego, Erika Gyengesi, Gerald Münch
August 2015, 10(8):1181-1185
DOI:10.4103/1673-5374.162686  PMID:26487830
Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible.
  49 4,191 1,121
The p75 neurotrophin receptor: at the crossroad of neural repair and death
Rick B Meeker, Kimberly S Williams
May 2015, 10(5):721-725
DOI:10.4103/1673-5374.156967  PMID:26109945
The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regulation of neurotrophin actions. Recently, the p75 neurotrophin receptor (p75 NTR ) has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by studies demonstrating 1) regulation of neural plasticity in the mature nervous system, 2) promotion of adult neurogenesis and 3) increased expression in neurons, macrophages, microglia, astrocytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and processes that support neural function. Upregulation of the p75 NTR under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-peptide p75 NTR ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75 NTR , studies summarized in this review highlight the immense potential for development of novel neuroprotective and neurorestorative therapies.
  39 4,210 1,150
Neuroinflammation and comorbidities are frequently ignored factors in CNS pathology
Raluca Elena Sandu, Ana Maria Buga, Adriana Uzoni, Eugen Bogdan Petcu, Aurel Popa-Wagner
September 2015, 10(9):1349-1355
DOI:10.4103/1673-5374.165208  PMID:26604877
Virtually all drug interventions that have been successful pre-clinically in experimental stroke have failed to prove their efficacy in a clinical setting. This could be partly explained by the complexity and heterogeneity of human diseases as well as the associated co-morbidities which may render neuroprotective drugs less efficacious in clinical practice. One aspect of crucial importance in the physiopathology of stroke which is not completely understood is neuroinflammation. At the present time, it is becoming evident that subtle, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease. Moreover, advanced aging and a number of highly prevalent risk factors such as obesity, hypertension, diabetes and atherosclerosis could act as "silent contributors" promoting a chronic proinflammatory state. This could aggravate the outcome of various pathological entities and can contribute to a number of subsequent post-stroke complications such as dementia, depression and neurodegeneration creating a pathological vicious cycle. Moreover, recent data suggests that the inflammatory process might be closely linked with multiple neurodegenerative pathways related to depression. In addition, pro-inflammatory cytokines could play a central role in the pathophysiology of both depression and dementia.
  39 2,709 538
Neuroprotective effects of berry fruits on neurodegenerative diseases
Selvaraju Subash, Musthafa Mohamed Essa, Samir Al-Adawi, Mushtaq A Memon, Thamilarasan Manivasagam, Mohammed Akbar
15th August 2014, 9(16):1557-1566
DOI:10.4103/1673-5374.139483  PMID:25317174
Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegenerative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kaempferol and tannin. In this review, we made an attempt to clearly describe the beneficial effects of various types of berries as promising neuroprotective agents.
  37 7,018 1,224
Advances in regenerative therapies for spinal cord injury: a biomaterials approach
Magdalini Tsintou, Kyriakos Dalamagkas, Alexander Marcus Seifalian
May 2015, 10(5):726-742
DOI:10.4103/1673-5374.156966  PMID:26109946
Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mechanism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing research interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaffold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerative/neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.
  37 5,115 1,325
Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer's disease mice
Yufang Yan, Tuo Ma, Kai Gong, Qiang Ao, Xiufang Zhang, Yandao Gong
15th April 2014, 9(8):798-805
DOI:10.4103/1673-5374.131596  PMID:25206892
In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippocampi of APP/PS1 transgenic Alzheimer's disease model mice. Immunofluorescence staining revealed that the number of newly generated (BrdU + ) cells in the subgranular zone of the dentate gyrus in the hippocampus was significantly higher in Alzheimer's disease mice after adipose-derived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU + /DCX + neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these findings, we propose that adipose-derived mesenchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer's disease mice, thereby facilitating functional recovery.
  35 4,211 841
Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries
Bo He, Zhaowei Zhu, Qingtang Zhu, Xiang Zhou, Canbin Zheng, Pengliang Li, Shuang Zhu, Xiaolin Liu, Jiakai Zhu
15th March 2014, 9(6):661-672
DOI:10.4103/1673-5374.130094  PMID:25206870
Objective: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. Data Sources: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. Study Selection: The following types of article were selected: (1) clinical trials describing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to investigate the patient and intervention factors associated with outcomes. Main Outcome Measures: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3 + or S4. Results: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were independent predictors of outcome after the repair of nerve injuries (P < 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. Conclusion: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.
  35 3,746 647
Dynamic reactive astrocytes after focal ischemia
Shinghua Ding
1st December 2014, 9(23):2048-2052
DOI:10.4103/1673-5374.147929  PMID:25657720
Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disorders including focal ischemic stroke, a leading cause of brain injury and human death. One of the prominent pathological features of focal ischemic stroke is reactive astrogliosis and glial scar formation associated with morphological changes and proliferation. This review paper discusses the recent advances in spatial and temporal dynamics of morphology and proliferation of reactive astrocytes after ischemic stroke based on results from experimental animal studies. As reactive astrocytes exhibit stem cell-like properties, knowledge of dynamics of reactive astrocytes and glial scar formation will provide important insights for astrocyte-based cell therapy in stroke.
  34 3,217 651
Emerging potential of exosomes for treatment of traumatic brain injury
Ye Xiong, Asim Mahmood, Michael Chopp
January 2017, 12(1):19-22
DOI:10.4103/1673-5374.198966  PMID:28250732
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.
  31 2,852 909
Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain
Sun Ryu, Seung-Hoon Lee, Seung U Kim, Byung-Woo Yoon
February 2016, 11(2):298-304
DOI:10.4103/1673-5374.177739  PMID:27073384
Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen NeuN, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ⁄ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.
  28 1,639 394
Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms
Zhi-yuan Guo, Xun Sun, Xiao-long Xu, Jiang Peng, Yu Wang
April 2015, 10(4):651-658
DOI:10.4103/1673-5374.155442  PMID:26170829
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.
  27 2,718 526
The potential of endogenous neurogenesis for brain repair and regeneration following traumatic brain injury
Dong Sun
1st April 2014, 9(7):688-692
DOI:10.4103/1673-5374.131567  PMID:25206873
Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individuals each year. It had been thought that recovery from such injuries is severely limited due to the inability of the adult brain to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been observed in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.
  27 2,703 634
Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage
Takeshi Okada, Hidenori Suzuki
February 2017, 12(2):193-196
DOI:10.4103/1673-5374.200795  PMID:28400792
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor (NF)-κB signaling among TLR4 signaling pathways as to the development of early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κB and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.
  25 1,607 435
Quercetin alleviates high glucose-induced Schwann cell damage by autophagy
Ling Qu, Xiaochun Liang, Bei Gu, Wei Liu
15th June 2014, 9(12):1195-1203
DOI:10.4103/1673-5374.135328  PMID:25206782
Quercetin can reverse high glucose-induced inhibition of neural cell proliferation, and therefore may have a neuroprotective effect in diabetic peripheral neuropathy. It is difficult to obtain primary Schwann cells and RSC96 cells could replace primary Schwann cells in studies of the role of autophagy in the mechanism underlying diabetic peripheral neuropathy. Here, we show that under high glucose conditions, there are fewer autophagosomes in immortalized rat RSC96 cells and primary rat Schwann cells than under control conditions, the proliferative activity of both cell types is significantly impaired, and the expression of Beclin-1 and LC3, the molecular markers for autophagy, is significantly lower. After intervention with quercetin, the autophagic and proliferative activity of both cell types is rescued. These results suggest that quercetin can alleviate high glucose-induced damage to Schwann cells by autophagy.
  25 2,808 536
Critical illness polyneuropathy and myopathy: a systematic review
Chunkui Zhou, Limin Wu, Fengming Ni, Wei Ji, Jiang Wu, Hongliang Zhang
1st January 2014, 9(1):101-110
DOI:10.4103/1673-5374.125337  PMID:25206749
Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease.
  24 8,654 2,680
Neurotrophic factors: from neurodevelopmental regulators to novel therapies for Parkinson's disease
Shane V Hegarty, Gerard W O'Keeffe, Aideen M Sullivan
1st October 2014, 9(19):1708-1711
Neuroprotection and neuroregeneration are two of the most promising disease-modifying therapies for the incurable and widespread Parkinson's disease. In Parkinson's disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neurotrophic factors play important regulatory roles in the development, survival and maintenance of specific neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinson's disease. Several neurotrophic factors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors: glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.
  24 2,232 353
Neurotrophic factors in Alzheimer's and Parkinson's diseases: implications for pathogenesis and therapy
Tuane Bazanella Sampaio, Anne Suely Savall, Maria Eduarda Ziani Gutierrez, Simone Pinton
April 2017, 12(4):549-557
DOI:10.4103/1673-5374.205084  PMID:28553325
Neurotrophic factors comprise essential secreted proteins that have several functions in neural and non-neural tissues, mediating the development, survival and maintenance of peripheral and central nervous system. Therefore, neurotrophic factor issue has been extensively investigated into the context of neurodegenerative diseases. Alzheimer's disease and Parkinson's disease show changes in the regulation of specific neurotrophic factors and their receptors, which appear to be critical for neuronal degeneration. Indeed, neurotrophic factors prevent cell death in degenerative processes and can enhance the growth and function of affected neurons in these disorders. Based on recent reports, this review discusses the main findings related to the neurotrophic factor support – mainly brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor – in the survival, proliferation and maturation of affected neurons in Alzheimer's disease and Parkinson's disease as well as their putative application as new therapeutic approach for these diseases management.
  24 2,193 676
Polysaccharides from Angelica sinensis alleviate neuronal cell injury caused by oxidative stress
Tao Lei, Haifeng Li, Zhen Fang, Junbin Lin, Shanshan Wang, Lingyun Xiao, Fan Yang, Xin Liu, Junjian Zhang, Zebo Huang, Weijing Liao
1st February 2014, 9(3):260-267
DOI:10.4103/1673-5374.128218  PMID:25206810
Angelica sinensis has antioxidative and neuroprotective effects. In the present study, we aimed to determine the neuroprotective effect of polysaccharides isolated from Angelica sinensis. In a preliminary experiment, Angelica sinensis polysaccharides not only protected PC12 neuronal cells from H 2 O 2 -induced cytotoxicity, but also reduced apoptosis and intracellular reactive oxygen species levels, and increased the mitochondrial membrane potential induced by H 2 O 2 treatment. In a rat model of local cerebral ischemia, we further demonstrated that Angelica sinensis polysaccharides enhanced the antioxidant activity in cerebral cortical neurons, increased the number of microvessels, and improved blood flow after ischemia. Our findings highlight the protective role of polysaccharides isolated from Angelica sinensis against nerve cell injury and impairment caused by oxidative stress.
  24 2,842 503
Diffuse axonal injury after traumatic cerebral microbleeds: an evaluation of imaging techniques
Jun Liu, Zhifeng Kou, Yongquan Tian
15th June 2014, 9(12):1222-1230
DOI:10.4103/1673-5374.135330  PMID:25206786
Previous neuropathological studies regarding traumatic brain injury have primarily focused on changes in large structures, for example, the clinical prognosis after cerebral contusion, intracerebral hematoma, and epidural and subdural hematoma. In fact, many smaller injuries can also lead to severe neurological disorders. For example, cerebral microbleeds result in the dysfunction of adjacent neurons and the disassociation between cortex and subcortical structures. These tiny changes cannot be adequately visualized on CT or conventional MRI. In contrast, gradient echo sequence-based susceptibility-weighted imaging is very sensitive to blood metabolites and microbleeds, and can be used to evaluate traumatic cerebral microbleeds with high sensitivity and accuracy. Cerebral microbleed can be considered as an important imaging marker for diffuse axonal injury with potential relevance for prognosis. For this reason, based on experimental and clinical studies, this study reviews the role of imaging data showing traumatic cerebral microbleeds in the evaluation of cerebral neuronal injury and neurofunctional loss.
  24 5,969 866
Resting-state functional connectivity abnormalities in first-onset unmedicated depression
Hao Guo, Chen Cheng, Xiaohua Cao, Jie Xiang, Junjie Chen, Kerang Zhang
15th January 2014, 9(2):153-163
DOI:10.4103/1673-5374.125344  PMID:25206796
Depression is closely linked to the morphology and functional abnormalities of multiple brain regions; however, its topological structure throughout the whole brain remains unclear. We collected resting-state functional MRI data from 36 first-onset unmedicated depression patients and 27 healthy controls. The resting-state functional connectivity was constructed using the Automated Anatomical Labeling template with a partial correlation method. The metrics calculation and statistical analysis were performed using complex network theory. The results showed that both depressive patients and healthy controls presented typical small-world attributes. Compared with healthy controls, characteristic path length was significantly shorter in depressive patients, suggesting development toward randomization. Patients with depression showed apparently abnormal node attributes at key areas in cortical-striatal-pallidal-thalamic circuits. In addition, right hippocampus and right thalamus were closely linked with the severity of depression. We selected 270 local attributes as the classification features and their P values were regarded as criteria for statistically significant differences. An artificial neural network algorithm was applied for classification research. The results showed that brain network metrics could be used as an effective feature in machine learning research, which brings about a reasonable application prospect for brain network metrics. The present study also highlighted a significant positive correlation between the importance of the attributes and the intergroup differences; that is, the more significant the differences in node attributes, the stronger their contribution to the classification. Experimental findings indicate that statistical significance is an effective quantitative indicator of the selection of brain network metrics and can assist the clinical diagnosis of depression.
  23 2,760 495
Key changes in denervated muscles and their impact on regeneration and reinnervation
Peng Wu, Aditya Chawla, Robert J Spinner, Cong Yu, Michael J Yaszemski, Anthony J Windebank, Huan Wang
15th October 2014, 9(20):1796-1809
The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle's residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.
  22 2,923 565
Mechanisms of secondary degeneration after partial optic nerve transection
Hong-Ying Li, Yi-Wen Ruan, Chao-Ran Ren, Qi Cui, Kwok-Fai So
15th March 2014, 9(6):565-574
DOI:10.4103/1673-5374.130093  PMID:25206855
Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associated with secondary degeneration including apoptosis, necrosis, autophagy, oxidative stress, excitotoxicity, derangements in ionic homeostasis and calcium influx. Glial cells, such as microglia, astrocytes and oligodendrocytes, have also been demonstrated to take part in the process of secondary injury. Partial optic nerve transection is a useful model which was established about 13 years ago. The merit of this model compared with other optic nerve injury models used for glaucoma study, including complete optic nerve transection model and optic nerve crush model, is the possibility to separate primary degeneration from secondary degeneration in location. Therefore, it provides a good tool for the study of secondary degeneration. This review will focus on the research progress of the mechanisms of secondary degeneration using partial optic nerve transection model.
  22 2,563 665
Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury
Linard Filli, Martin E Schwab
April 2015, 10(4):509-513
DOI:10.4103/1673-5374.155425  PMID:26170799
Axonal regeneration and fiber regrowth is limited in the adult central nervous system, but research over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance fiber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of structural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The formation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identified as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the existence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic interventions (e.g., fiber-growth enhancing interventions, rehabilitation). This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of propriospinal circuits to maximize functional recovery after spinal cord injury.
  22 4,961 1,387
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