Effect of focal cerebral infarctions on lesional RhoA and RhoB expression

Christine Brabeck, Michel Mittelbronn, Kubrom Bekure, Richard Meyermann, Hermann J. Schluesener, Jan M. Schwab*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    35 Citations (Scopus)

    Abstract

    Background: Blockade of the small GTPase Rho (ras homology protein) or of its downstream target Rho-associated kinase has been shown to promote axon regeneration in vitro and in vivo and to improve functional recovery after experimental central nervous system lesions. Objective: To determine the expression patterns of RhoA and RhoB after focal cerebral infarction (FCI) and to assess whether Rho is a possible target for pharmacologic intervention. Methods: Expression patterns of RhoA and RhoB were investigated in brain tissue specimens from 22 patients who died after FCI - clinically appearing as stroke - and were compared with those in brain tissue specimens from 4 neuropathologically unaffected controls by immunohistochemical analysis. Results: Compared with control brains, a significant lesional up-regulation of RhoA and RhoB was observed beginning 2 to 10 days after ischemia and continuing for 4 to 38 months after FCI (P<.001). The cellular sources of both molecules included polymorphonuclear granulocytes, monocytes/macrophages, and reactive astrocytes. Neuronal RhoB expression was detected in the very early stages after FCI and in some cases in the later stages adjacent to the lesion. Conclusions: Inhibition of Rho is a promising lead for the development of new pharmacologic interventions in FCI. Because the observed up-regulation of RhoA and RhoB was still detectable months after FCI, we speculate that even delayed treatment with Rho inhibitors might be a therapeutic option.

    Original languageEnglish
    Pages (from-to)1245-1249
    Number of pages5
    JournalArchives of Neurology
    Volume60
    Issue number9
    DOIs
    Publication statusPublished - 1 Sept 2003

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