Excitotoxic striatal lesion induces inflammation, astrogliosis, axonal injury, and myelin damage in the rat internal capsule: Implications for regenerative medicine

JOURNAL/rmrep/04.03/02273995-202604000-00002/figure1/v/2026-03-19T111208Z/r/image-tiff Objectives: The internal capsule is an important white matter structure involved in motor control and sensory information processing. Damage to this region has been associated with motor deficits and diverse neurological disorders. In experimental models, striatal excitotoxic lesions can trigger secondary degeneration in adjacent white matter tracts; however, the spatiotemporal dynamics of inflammatory responses, axonal injury, and myelin impairment in the internal capsule remain poorly understood. In this context, we characterized white matter alterations in the internal capsule following focal striatal excitotoxic injury in Wistar rats. Methods: Animals received intrastriatal injection of N-methyl-D-aspartate and were analyzed at 1, 3, and 7 post-lesion days. Histological and immunohistochemical analyses assessed inflammation (neutrophils – Martine Bernardes-Silva-1, macrophages – anti-CD68 antibody), gliosis (astrocytes - glial fibrillary acidic protein), axonal damage (β-amyloid precursor protein), and myelin integrity (myelin basic protein). Results: Neutrophilic inflammation peaked at 1 post-lesion day, followed by macrophage accumulation at 3 post-lesion days, and marked astrocytosis at 7 post-lesion days. Myelin rarefaction and progressive disruption were most evident at 7 post-lesion days, coinciding with pronounced axonal pathology. Conclusion: These findings demonstrate that striatal excitotoxicity induces a cascade of inflammatory, astrogliosis, axonal, and myelin alterations in the internal capsule, underscoring the vulnerability of remote white matter tracts to secondary injury. Beyond reinforcing the pathophysiology of white matter damage, this model provides a framework for exploring therapeutic and regenerative medicine approaches that aim at mitigating axonal degeneration and promoting myelin repair.