TY - JOUR
T1 - Effect of focal cerebral infarctions on lesional RhoA and RhoB expression
AU - Brabeck, Christine
AU - Mittelbronn, Michel
AU - Bekure, Kubrom
AU - Meyermann, Richard
AU - Schluesener, Hermann J.
AU - Schwab, Jan M.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0041920590&partnerID=8YFLogxK
U2 - 10.1001/archneur.60.9.1245
DO - 10.1001/archneur.60.9.1245
M3 - Article
C2 - 12975290
AN - SCOPUS:0041920590
SN - 0003-9942
VL - 60
SP - 1245
EP - 1249
JO - Archives of Neurology
JF - Archives of Neurology
IS - 9
ER -