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Effect of focal cerebral infarctions on lesional RhoA and RhoB expression
Christine Brabeck1, Michel Mittelbronn, Kubrom Bekure
1Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
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.
Insights
RhoA and RhoB proteins are upregulated after focal cerebral infarction (FCI), suggesting Rho inhibition may be a therapeutic target for stroke recovery, even with delayed treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Blockade of the small GTPase Rho (ras homology protein) or Rho-associated kinase promotes axon regeneration and functional recovery in central nervous system injuries.
- Rho signaling pathways are implicated in neuronal repair mechanisms.
Purpose of the Study:
- To investigate the expression patterns of RhoA and RhoB following focal cerebral infarction (FCI).
- To evaluate the potential of Rho as a therapeutic target for pharmacological intervention in stroke.
Main Methods:
- Immunohistochemical analysis of brain tissue from 22 patients with FCI (stroke) and 4 healthy controls.
- Assessment of RhoA and RhoB expression levels and cellular localization post-ischemia.
Main Results:
- Significant upregulation of RhoA and RhoB was observed in lesional areas from 2 to 10 days and up to 38 months after FCI compared to controls.
- Cellular sources included granulocytes, monocytes/macrophages, and reactive astrocytes; neuronal RhoB was detected early and late post-FCI.
- Expression changes were statistically significant (P<.001).
Conclusions:
- Rho inhibition presents a promising strategy for developing novel pharmacological treatments for FCI.
- The sustained upregulation of RhoA and RhoB months after FCI suggests that delayed therapeutic interventions targeting Rho may be viable.