Lesional expression of RhoA and RhoB following traumatic brain injury in humans.
Inhibition of the small GTPase Rho or of its downstream target Rho-associated kinase (ROCK) has been shown to promote axon regeneration and to improve functional recovery following traumatic CNS lesions in the adult rat. In order to determine the expression pattern of RhoA and RhoB following human traumatic brain injury (TBI) and to assess whether Rho is a possible target for pharmacological intervention in humans, we investigated expression patterns of RhoA and RhoB in brain specimens from 25 patients who died after closed TBI in comparison to brain tissue derived from four neuropathologically unaffected control patients by immunohistochemistry. A highly significant lesional upregulation of both RhoA and RhoB was observed beginning several hours after the traumatic event and continuing for months after TBI. The cellular sources of both molecules included polymorphonuclear granulocytes, monocytes/macrophages, and reactive astrocytes. Additionally, expression of RhoA was also detected in neuronal cells in some of the cases. From our data, we conclude that inhibition of Rho is a promising mechanism for the development of new pharmacological interventions in human TBI. As the observed upregulation of RhoA and RhoB was still detectable months after TBI, we speculate that even delayed treatment with Rho inhibitors might be a therapeutic option.
Brabeck
Christine
C
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Beschorner
Rudi
R
Conrad
Sabine
S
Mittelbronn
Michel
M
Bekure
Kubrom
K
Meyermann
Richard
R
Schluesener
Hermann J
HJ
Schwab
Jan M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein