RESUMEN
SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.
RESUMEN
Objective To research the prohibitin2 (PHB2) expression and cellular localization in the rat brain cortex after traumatic brain injury (TBI),and explore its relationship with astrocyte proliferation and neuron apoptosis.Methods TBI rat models were established by knife injurying the brain.Western blotting was used to detect the PHB2 expression variation trend in the brain cortex.Immunohistochemical method was used to detect the distribution of PHB2 in damaged cerebral cortex,and immunofluorescence was applied to research the PHB2 expression changes and cellular localization in the rat brain cortex after TBI,and explore its relationship with astrocyte proliferation and neuron apoptosis.Results (1) The TBI models were established successfully;12 h after TBI,the PHB2 expression started to increase obviously,and PHB2 expression reached to its peak level 5 d after TBI.(2)The PHB2 expression in the cortex of TBI rats was significantly increased as compared with that in the sham-operated group,control group and contralateral side of TBI rats.(3) PHB2 mainly located at the astrocytes and neurons of the cerebral cortex after TBI.(4) Co-localization was noted in astrocytes and cell proliferation marker PCNA,and in PHB2 and PCNA,which indicated that proliferation of astrocytes existed and PHB2 involved in the proliferation.(5) Co-localization was noted in astrocytes and cell apoptosis marker A-caspase-3,and in PHB2 and A-caspase-3,which indicated that TBI induced cell apoptosis,and PHB2 involved in the apoptosis.Conclusion PHB2 has a high expression in the cerebral cortex of rats after TBI,and these changes are related to astrocyte proliferation and neuronal apoptosis.