Spinal cord injury (SCI) triggers immediate and widespread pathophysiological changes not only at the site of impact but also beyond it, including alterations in remote cortical regions. Here, we report early astrocytic changes in the cerebral cortex following SCI at birth, identified using two specific glial markers in an innovative in vitro model of the entire central nervous system (CNS) isolated from neonatal rats. Immunohistochemical analyses revealed a significant reduction in cortical astrocyte density, first observed in the dorsomedial motor cortex (M1) within 25 min post-injury, followed by progressive changes in the ventrolateral somatosensory cortex (S1/S2) at 2 h post-injury. These findings indicate that SCI initiates a rapid and dynamic reorganization of cortical glial networks, shedding new light on astrocytic responses to spinal trauma.