Ultrastructural neuroprotection by intrathecal interleukin-6 antagonism in a rat model of permanent focal cerebral ischemia.

This study aimed to determine whether intrathecal administration of an interleukin-6 (IL-6) neutralizing antibody could reduce ultrastructural neuronal and vascular damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Forty male Wistar rats were randomly assigned to four groups: Control, Sham-operated, Occlusion (MCAO + saline), and Treatment (MCAO + anti-rat IL-6 antibody). One week later, ischemic core brain tissue was processed for transmission electron microscopy to evaluate neuronal, axonal, and microvascular integrity. The Occlusion group showed severe ischemic injury, including mitochondrial swelling with cristolysis, cytoplasmic vacuolization, axonal edema, endothelial swelling, and perivascular astrocyte edema. By contrast, the Treatment group demonstrated marked ultrastructural preservation. Endothelial swelling and perivascular edema were reduced, neuronal nuclei were more preserved, and myelin sheath separation in white matter fibers was less pronounced than in the Occlusion group. Direct intrathecal IL-6 blockade was associated with qualitative cellular-level neuroprotection after permanent focal cerebral ischemia. The treatment attenuated inflammatory vascular injury and white matter damage, supporting IL-6 as a potential therapeutic target for limiting secondary stroke injury.