Reactive Aistrocytes As A Target For Treatment Of Spinal Cord Injury

Spinal cord injury often results in loss of sensation and paralysis that are irreversible. This is in part because CNS neurons have a poor intrinsic capacity for growth, but also because injured axons encounter a series of inhibitory microenvironment that are non-permissive for growth. Reactive astrogliosis, whereby astrocytes undergo varying molecular and morphological changes, is a ubiquitous but poorly understood hallmark of all central nervous system pathologies. Recent studies provide compelling evidence that reactive astrogliosis can exert both beneficial and detrimental effects in a context-dependent manner determined by specific molecular signaling cascades.Thus, astrogliosis is an appealing target for therapeutic interventions aimed at promoting nervous tissue preservation and functional repair. In the present study, we explore the effects of reactive astrogliosis after CNS damage especially SCI and the underlying mechanisms. Our studies indicated that:(1) TNF-α produced by reactive astrocytes in glial scar inhibits the maturation of OPCs via TNFR1;(2) Ethyl pyruvate, a pyruvate derivative, inhibits the activation astrocytes and the formation of glial scar, which contributes to axon regeneration and functional recovery after SCI;(3) nitidine treatment could attenuate reactive astrogliosis and increase spinal tissue sparing and improved functional recovery. These results will be beneficial for us to understand the mechanisms of reactive astrogliosis and as a significant cue to open new avenues for treating SCI.