An investigation into the early stages of the inflammatory response following ibotenic acid-induced neuronal degeneration.

Injection of the excitatory neurotoxin ibotenic acid into the septum produces rapid destruction of neuronal cell bodies and accompanying gliosis. We have previously shown that following ibotenate-induced cell death this may also result in damage to healthy axons en passage (Coffey et al., Neurosci. Lett. 84, 178-184, 1988). We suggested that the axonal damage resulted from non-specific damage by recruited inflammatory cells. In this study we have further examined the phenotype of the cells involved in the inflammatory response in the rat. Immunocytochemical identification of cells in the region of the lesion site identifies them as being of haematopoitic origin and most of them have the phenotype of macrophages. The dramatic increase in their number following an ibotenate lesion is sensitive to irradiation of the body providing evidence that the majority are blood derived. The inflammatory response is accompanied by a loss of myelin and a breakdown of the blood-brain barrier in the region of the lesion site. We have shown that these two effects are consequences of the inflammatory response since reduction in the inflammatory response by prior irradiation will abrogate these two effects.