Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Advance in mechanisms of glial scarring after stroke and intervention of traditional Chinese medicine / 中国中药杂志

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.

Response of NG2 positive cells and other glial cells in the microenvironment of facial nucleus after facial nerve axotomy / 解放军医学杂志

Objective To study the response of NG2 positive and other glial cells in the facial nucleus after facial nerve axotomy,and explore the changes of the microenvironment in the facial nucleus.Methods Rat facial nerve axotomy models were established.Immunofluorescence double staining,and immunohistochemical staining combined with cresyl violet staining were used to observe the response of NG2 cells and other glial cells,and Western blotting was performed to test NG2 protein expression in facial nucleus at postoperative 1,2,7,14,and 28 days.Results Microglia formed dense circles closely around the injured neurons.Astrocytes formed wreath-like structure near the injured neurons.NG2 protein in the injured nucleus has a regular timephase change and NG2 positive cells showed an extensive detachment of synaptic terminals on the damaged neurons after facial nerve axotomy.NG2 cell response was almost the same as microglia.Conclusions All kinds of glial cells may be involved in the formation of glial scar.NG2 positive cells could insulate the damaged neurons against the potential damage from the excitatory input.

Sensory Axon Regeneration: A Review from an in vivo Imaging Perspective

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.

Effects of visfatin on NG2 cells following cerebral ischemia/reperfusion injury in rats / 第二军医大学学报

Objective To investigate the effect of visfatin on the NG2 cell number in the brain of normal rats and rats with cerebral ischemia/reperfusion (I/R) injury. Methods Transient focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) and a monofilament suture via intraluminal approach in rats. Thirty adult male Wistar-Kyoto rats were randomly divided in to four groups, namely, a sham operation group (Sham), a cerebral I/R model group(MCAO), Sham+FK866(a specific inhibitor of visfatin) group, and cerebral I/R+FK866 group. Animats nn the latter two groups were intragastsically given FK866 (1 mg/[kg • d]) for a consecutive of 14 days; Sham operation or MCAO was pefformed at the 7th day of FK866 treatment. The NG2 cells were observed by immunofluorescence staining in animal brains at the 7th day after surgery. Results There was no signficant difference in NG2 cell numbeis between the Sham group and Sham + FK866 group. Cerebral I/R model group had significantly less NG2 cells in the core region of infarction(P<0. 01) and significantly more in the penumbra area (P<0. 01) compared with the Sham group, with no significant change in the contralateral side. The NG2 cell numbers were not significantly different between the cerebral I/ R model group and cerebral I/R + FK866 group in the above mentioned areas. Conclusion Inhibition of visfatin shows no noticeable effect on NG2 cell number in the brains of normal and cerebral I/R rats, indicating that the neuroprotective effect of visfatin is not assoiiated with NG2 cells.

NG2 proteoglycan promotes mesangial cells proliferation and extracellular matrix production / 中华肾脏病杂志

Objective To explore the role of NG2 proteoglycan in the pathogenesis of glomerulosclerosis. Methods Eukaryotic expression vectors carrying the small hairpin RNA (shRNA) for NG2 mRNA , named as Psilencer-NG2, was constructed. Then, rat mesangial cells (RMC) were transfeeted with Psilencer-NG2, Psilencer-NC (negative control), pcDNA/NG2 (NG2 over-expressive vector) and empty vector pcDNA 1 respectively. The expression of endogenous NG2 in RMCs was examined by real-time PCR and Western blotting. Cell proliferation was analyzed by MTT assay and flow cytometry. The expression of laminin was detected by real-time PCR. Results Transfection of pcDNA/NG2 into HBZY-1 cells resulted in over-expression of NG2 mRNA and protein (P<0.05, P<0.05). Transfection of Psilencer-NG2 led to reduced expression of NG2 mRNA and protein (P<0.01, P<0.01). The expression of laminin β1 significantly increased due to overexpression of NG2 and decreased by treating with NG2 siRNA. According to MTT assay, overexpreasion of NG2 significantly stimulated the proliferation of mesangial cells while NG2 silencing inhibited it. NG2 increased the cell number in S phase and decreased the cell number in G0/G1 phase, while silencing NG2 induced the decrease of cell number in S phase and the increase of cell number in G0/G1 phase. Conclusion NG2 actively participates in the pathogenesis of glomerulosclerosis by stimulating proliferation of RMCs and increasing the deposition of ECM.

Postnatal development and perinatal electrophysiological characteristics of oligodendrocyte precursor cell in rats / 第三军医大学学报

Objective To observe the postnatal development and perinatal electrophysiological characteristics of oligodendrocyte precursor cell (OPC) in rats. Methods Immunohistochemistry and Western blot were applied to determine the expression of NG2 OPC in cerebral cortex and hippocampus at various developmental stages of SD rats. Electrophysiological characteristics of OPC were also recorded in slices of 7-day rats. Results The majority of hippocampal and cerebral OPC exhibited stellate shape,a small cell body with a few processus. Total population of the NG2 immunopositive OPC was numerous at P7d in cerebral cortex and hippocampus. OPC expressed in adult rats with slightly more quantity. Moreover,OPC in hippocampus of P7d rats typically exhibited small inward sodium current and weak active responses,whereas only outward potassium current and inactive responses were recorded in white matter OPC of P7d rats. Conclusion Total population of OPC and relative optical density of NG2 are the highest in P7d rats at the postnatal developmental stages. OPC in cerebrum and hippocampus of P7d rats displays electrophysiological heterogeneity.

Morphological localization of NG2 positive cells in the brain of adult rats / 第三军医大学学报

Objective To observe the localization of NG2 positive cells and morphological character in the brain of adult rats. Methods Immunohistochemical method was applied to determine the expression of NG2 positive cells in the cerebrum cortex, hippocampus, dentate gyrus, thalamencephalon and hypothalamus of adult rats. Image analysis program Image Pro Plus 5.0 was used to count the positive cells and for statistic analysis. Results NG2 positive cells were strongly expressed in multiple brain regions of adult rats, of which strongest signals were centralized in gray and white matter of cerebral cortex, hippocampus, dentate gyrus, thalamic subventricular zone and hypothalamic periventricular region. The NG2 positive cells were seen with abundant process arborization which bifurcated two or more times. The soma of NG2 positive cell displays a star-like morphology with different shapes in the gray and white matter of cerebrum cortex. Conclusion NG2 positive cells are numerous in adult rat brain and display the special glial with a stellate morphology.

THE RESEARCH PROGRESS ON NG2 GLIAL CELLS / 解剖学报

Objective To review the physiological characters and potential function of chondroitin sulphate proteoglycan,CSPG(NG2) glial cells in the central nervous system. Methods In conclusion of the NG2 glial properties and the global, novel researches on NG2 cells. Results Cells that express the NG2 proteoglycan comprise a unique population of glial cells in the central nervous system.Study on their role in the CNS becomes more and more popular.Previous researches mainly focus on the differentiation and distinction.Now the relationship between NG2 glial cells and neurons,and the synaptic plasticity is becoming a hot topic.Conclusion This review referred the research development of NG2 glial cells,including the differentiation,migration,their interaction with neurons,and the potential role in glial cell regeneration in disease systematically.