INFLAMMATION AND GLIAL RESPONSES IN ISCHEMIC BRAIN-LESIONS

Focal cerebral ischemia elicits a strong inflammatory response involvi ng early recruitment of granulocytes and delayed infiltration of ische mic areas and the boundary zones by T cells and macrophages. Infiltrat ion of hematogenous leukocytes is facilitated by an upregulation of th e cellular adhesion molecules P-selectin, intercellular adhesion molec ule-1 and vascular adhesion molecule-1 on endothelial cells. Blocking of the leukocyte/endothelial cell adhesion process significantly reduc es stroke volume after transient, but not permanent middle cerebral ar tery occlusion. In the infarct region microglia are activated within h ours and within days transform into phagocytes, Astrocytes upregulate intermediate filaments, synthesize neurotrophins and form glial scars. Local microglia and infiltrating macrophages demarcate infarcts and r apidly remove debris. Remote from the lesion no cellular infiltration occurs, but astroglia and microglia are transiently activated. Astrocy tic activation is induced by spreading depression. In focal ischemia n eurons die acutely by necrosis and in a delayed fashion by programmed cell death, apoptosis. Proinflammatory cytokines such as tumor necrosi s factor-alpha and interleukin-1 beta are upregulated within hours in ischemic brain lesions. Either directly or via induction of neurotoxic mediators such as nitric oxide, cytokines may contribute to infarct p rogression in the post-ischemic period. On the other hand, inflammatio n is tightly linked with rapid removal of debris and repair processes. At present it is unclear whether detrimental effects of inflammation outweigh neuroprotective mechanisms or vice versa. In global ischemia inflammatory responses are limited, but micro- and astroglia are also strongly activated. Glial responses significantly differ between brain regions with selective neuronal death and neighbouring areas that are more resistent to ischemic damage, (C) 1998 Elsevier Science Ltd. All rights reserved.