Effect of focal cerebral infarctions on lesional RhoA and RhoB expression.

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.