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Immunological Aspects of Ischaemic Stroke

Therapeutic Implications

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Abstract

There is increasing evidence that inflammatory processes play a central role in atherosclerosis and in secondary infarct growth after focal cerebral ischaemia. Focal cerebral ischaemia is often the result of arterio-arterial thromboembolism arising from plaques in the internal carotid artery (ICA). In the ICA, the extent of inflammatory infiltration by T cells and macrophages, and the expression of matrix metalloproteinase-9 in high grade stenoses, correlate with clinical features of plaque destabilisation.

Within the CNS, focal ischaemia induces a strong inflammatory response, with recruitment of granulocytes, T cells and macrophages which is facilitated by early upregulation of cell adhesion molecules. In experimental animals, anti-adhesion strategies have led to a dramatic reduction of stroke volumes; however, these strategies have failed to be effective in humans.

‘Immunological’ transcription factors and inducible nitric oxide synthase are upregulated in focal ischaemia and contribute to secondary infarct growth between 24 and 72 hours after the initial insult. The cytokines interleukin-1β and tumour necrosis factor-α are induced prior to inflammation. Functionally, these cytokines exert both neurotoxic and neuroprotective effects after cerebral ischaemia.

At present, immunological strategies targeted at a single immunomodulator for the treatment of stroke are hampered by an incomplete understanding of the complex cellular and molecular interactions that lead to divergent functional effects of inflammatory cells and immunological mediators after focal ischaemia.

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Acknowledgements

The authors’ work cited in this review was supported by the Deutsche Forschungsgemeinschaft (SFB 194, B6). Dr Stoll holds a Hermann- and Lilly-Schilling professorship.

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Authors and Affiliations

  1. Department of Neurology, Heinrich-Heine-Universität, Moorenstr. 5, 40225, Düsseldorf, Germany

    Guido Stoll, Sebastian Jander, Mario Siebler & Michael Schroeter

  2. The Center for Biological and Medical Research, Heinrich-Heine-Universität, Düsseldorf, Germany

    Guido Stoll

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  1. Guido Stoll
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  2. Sebastian Jander
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  3. Mario Siebler
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  4. Michael Schroeter
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Correspondence to Guido Stoll.

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Stoll, G., Jander, S., Siebler, M. et al. Immunological Aspects of Ischaemic Stroke. Mol Diag Ther 14, 213–228 (2000). https://doi.org/10.2165/00023210-200014030-00004

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