TY - JOUR
T1 - Lesional expression of RhoA and RhoB following traumatic brain injury in humans
AU - Brabeck, Christine
AU - Beschorner, Rudi
AU - Conrad, Sabine
AU - Mittelbronn, Michel
AU - Bekure, Kubrom
AU - Meyermann, Richard
AU - Schluesener, Hermann J.
AU - Schwab, Jan M.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
KW - Pharmacological target
KW - Regeneration
KW - Rho GTPases
KW - Tissue remodeling
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=3042775013&partnerID=8YFLogxK
U2 - 10.1089/0897715041269597
DO - 10.1089/0897715041269597
M3 - Article
C2 - 15253798
AN - SCOPUS:3042775013
SN - 0897-7151
VL - 21
SP - 697
EP - 706
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 6
ER -