The kinase inhibitory region of SOCS3 attenuates reactive astrogliosis and astroglial scar in mice after traumatic brain injury.

Traumatic brain injury (TBI) leads to reactive astrogliosis that impedes neural repair/regeneration. It has been proven that SOCS3 attenuates astrocyte activation by inhibiting the JAK2-STAT3 pathway. However, whether the kinase inhibitory region (KIR) of SOCS3 can be directly applied to mediate astrocyte activation after TBI is not clear. The present study aimed at investigating the inhibitory effect of KIR on reactive astrogliosis and its potential neuroprotection after TBI insult. For this purpose, A TBI model was developed by the free impact of heavy objects in adult mice. KIR was linked to the TAT peptide (TAT-KIR) to facilitate cell membrane penetration and intracranially injected into the cerebral cortex adjacent to the TBI lesion. Then reactive astrogliosis, activity of JAK2-STAT3 pathway, neuron loss, and function deficit were observed. Our results showed a decrease in neuron loss and an improvement in neural function. Meanwhile, Intracranial injection of TAT-KIR in TBI mice demonstrated a reduction of GFAP-positive astrocytes as well as C3/GFAP double-labeled A1 reactive astrocytes. Western blot analysis illustrated that the activity of the JAK2-STAT3 pathway was significantly inhibited by TAT-KIR. We conclude that exogenous treatment TAT-KIR, through suppression of JAK2-STAT3 activity, inhibits TBI -induced reactive astrogliosis induced, thereby alleviating the loss of neurons and relieving the neural function deficit. This investigation suggests that TAT-KIR could be a potential therapeutic strategy for enhancing neural regeneration following.