Differential patterns of inflammatory response, axonal damage and myelin impairment following excitotoxic or ischemic damage to the trigeminal spinal nucleus of adult rats

Inflammatory response, axonal damage and demyelination are important components of the pathophysiology of acute neuro degenerative diseases. We have investigated the outcome of these pathological events following an excitotoxic or an ischemic damage to the spinal nucleus of adult rats at 1 and 7 days postinjury. Microinjections of 80 nmol of NMDA or 40 pmol of endothelin-1 into the rat spinal nucleus induced differential histopathological events. NMDA injection induced intense tissue loss in the gray matter (GM) without significant tissue loss in the white matter (WM). There was a mild inflammatory response, with recruitment of a few neutrophils and macrophages. Axonal damage was present in the GM following NMDA injection, with negligible axonal damage in the WM. Myelin impairment was apparent: at 7 days. Microinjections of endothelin-1 into the same region induced lesser tissue loss than NMDA injections, concomitant with an intense inflammatory response characterized by recruitment of macrophages, but not of neutrophils. There were more axonal damage and early myelin impairment after endothelin-1 injection. These results were confirmed by quantitative analysis. Microcysts were present in the WM of the trigeminothalamic tract at 7 days following injection of endothelin-1. These results show that an ischemic damage to the spinal nucleus affects both GM and WM with more bystander inflammation, axonal damage and myelin impairment, while excitotoxic damage induces effects more restricted to the GM. These pathological events may occur following acute damage to the human brain stem and can be an important contributing factor to the underlying functional deficits. (C) 2007 Elsevier B.V. All rights reserved.