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Third-party-funded project

Title:
Immunological pathomechanisms of focal cerebral ischemia

Project management at the University of Würzburg:

Participating scientists:

Abstract:
Immune mediators are critically involved in infarct growth after cerebral ischemia. We have analysed patterns of microglial activation and leukocyte infiltration in two experimental models of cerebral ischemia (occlusion of the middle cerebral artery (MCAO) and photothrombosis), and for the first time could delineate intrinsic microglial responses from hematogenous macrophage influx. Further phenotypical analysis revealed a novel and unusual population of CD8+ microglia/macrophages that was exclusively associated with areas of necrotic tissue damage (Schroeter et al., 1999;2001). Surprisingly, the proinflammatory cytokines TNF and IL-1 were upregulated prior to leukocyte infiltration in ischemic brain areas (Jander et al., 2000), while others such as interleukin-18 were strongly associated with inflammation (Jander et al., 2002). These cytokines most likely are neurotoxic in the infarct area and boundary zone. Interestingly, TNF and IL-1 were also induced in remote ipsilateral cortex areas devoid of neuronal cell death. These remote responses could be abolished by pretreatment with the NMDA-receptor antagonist MK-801, and mimicked in naive animals by KCl-induced spreading depression (SD) (Jander et al., 2001). SD are neuroprotective. Our study for the first time shows that an ion shift is sufficient to induce cytokine induction in the brain.

Key words:
    ischemic stroke
    inflammation
    neuroprotection

Projekt period: from 01.2000 to 12.2002

Publications: