mTOR Activation Is Required for the Proliferation of Reactive Astrocytes in the Hippocampus During Traumatic Brain...

Astrocytes undergo pronounced reactivity during traumatic brain injury (TBI); however, the temporal dynamics of this response and the signaling mechanisms regulating astrocyte proliferation remain incompletely defined. In this study, we characterized the spatiotemporal profile of astrocyte reactivity and proliferation in the hippocampus during TBI and investigated the involvement of mammalian target of rapamycin complex 1 (mTORC1) signaling in these processes. Using a mouse model of TBI, we found that injury triggered a rapid astrocytic response in the hippocampus, characterized by increased glial fibrillary acidic protein (GFAP) expression and morphological hypertrophy as early as 4 h post-injury. Astrocyte proliferation emerged subsequently, peaked during the acute phase (48 and 72 h), and declined to baseline levels at 7 days post-trauma, indicating a transient proliferative response during TBI. Concurrently, mTORC1 signaling was robustly activated in reactive astrocytes in the hippocampus and was specifically associated with proliferative reactive astrocytes during injury. Pharmacological inhibition of mTORC1 signaling with rapamycin significantly reduced reactive astrocyte proliferation during TBI without altering astrocytic hypertrophy. Together, these findings demonstrate that TBI induces a rapid but transient astrocyte activation and proliferation response in the hippocampus and that mTORC1 activation is required for the proliferation, but not the hypertrophic activation, of reactive astrocytes during traumatic brain injury.