Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*

Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.
Animals ; Astrocytes/metabolism* ; Brain/metabolism* ; Brain Injuries/pathology* ; Cytokines/metabolism* ; Forensic Medicine/methods* ; Gene Expression Regulation/drug effects* ; Humans ; Metallothionein/physiology* ; Neurons/metabolism* ; Neuroprotective Agents/pharmacology* ; Oxidative Stress/drug effects*

Human central neurocytoma is a kind of the brain tumors that are usually found in anterior part of the lateral ventricles. In this study, we established conditions that allowed proliferation of neurocytoma cells culture and analyzed characteristics of neurocytoma cells in vitro. For in vitro, a condition that used for culturing neural stem cells and contained basic fibroblast growth factor (bFGF) provided high proliferation. RT-PCR analaysis showed that nestin was found in neurocytoma cells, indicating that the neurocytomas possess neural stem cell properties. Interestingly, treatment of neurocytoma cells with forskolin increased expression of glial fibrillary acidic protein with a concomitant decrease in the nestin expression. Forskolin also induced morphological changes of neurocytoma cells to adopt an astrocyte-like phenotype. The results suggest that neurocyotma cells may have properties of multipotent neural stem cells.
Animals ; Astrocytes/cytology/*physiology ; Cell Differentiation/*drug effects ; Cell Proliferation ; Cell Shape ; Fibroblast Growth Factor 2/pharmacology ; Forskolin/*pharmacology/*therapeutic use ; Humans ; Intermediate Filament Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; Neurocytoma/*drug therapy/pathology ; Research Support, Non-U.S. Gov't ; Tumor Cells, Cultured

OBJECTIVETo investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca(2+) reperfusion.

METHODSThe apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca(2+) reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed.

RESULTSBoth the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes (39.73%+/-4.16%) were higher than the astrocytes (19.64%+/-4.67%) 24 hours after Ca(2+) reperfusion. The TUNEL positive cells were 13.6+/-1.82 and 21.4+/-1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca(2+) reperfusion.

CONCLUSIONSThe astrocytes and oligodendrocytes are similar wi th the development rules on apoptosis and have different susceptiveness to the situation.

Animals ; Apoptosis ; drug effects ; physiology ; Astrocytes ; cytology ; pathology ; physiology ; Calcium ; physiology ; Cells, Cultured ; Flow Cytometry ; In Situ Nick-End Labeling ; Oligodendroglia ; cytology ; pathology ; physiology ; Rats ; Rats, Wistar

Hydrogen peroxide is considered to be a dose- and time-dependent mediator in apoptotic and necrotic death. In this study, we examined the signaling of the E6 and E7 proteins with respect to apoptosis or necrosis after H2O2 injury using an in vitro model with overexpressed E6 or E7 genes. For this purpose, the E6 and E7 gene expressing astrocytes were exposed to 0.01 mM and 0.2 mM H2 O2 solutions. Twenty- four hours after treatment with the lower dosage(0.01 mM H2O2), control, E6-expressing cells suffered about 45% injury and LXSN-expressi ng cells decreased by 67% as assessed by LDH release. However, E7-expressing cells showed less injury, resulting in 20-30% of LDH release. Astrocytes expressing E6, E7, LXSN and mock-infected cells showed a typical apoptotic death patter n on the DNA gel after treatment with a low-dose of H2O2 (0.01 mM), however the y died from necrotic death after a high-dose (0.2 mM) H2O2. Overexpression of HPV-E7 genes protected the cells from apoptotic death after a low-dose of H2O2 and from necrotic death after a high-dose of H2O2, while the overexpression of E 6 genes from the necrotic death. E7 expressing astrocytes showed higher catalas e activity and the levels of E2F protein surged more than 100-folds compared with the control astrocytes. We believe that the activity of E7 protein to protect astrocytes from H2O2 injury was at least partly due to increased catalase, a scavenger protein.
Animal ; Apoptosis/*physiology ; Astrocytes/*drug effects/pathology/*physiology ; Cells, Cultured ; Hydrogen Peroxide/*pharmacology ; Mice ; Necrosis ; Oncogene Proteins, Viral/*genetics/*physiology ; Oxidants/*pharmacology ; Signal Transduction/physiology