Dexamethasone suppresses infiltration of RhoA+ cells into early lesions of rat traumatic brain injury.
Inflammatory cell infiltration is a major part of secondary tissue damage in traumatic brain injury (TBI). RhoA is an important member of Rho GTPases and is involved in leukocyte migration. Inhibition of RhoA and its downstream target, Rho-associated coiled kinase (ROCK), has been proven to promote axon regeneration and function recovery following injury in the central nervous system (CNS). Previously, we showed that dexamethasone, an immunosuppressive corticosteroid, attenuated early expression of three molecules associated with microglia/macrophages activation following TBI in rats. Here, the effects of dexamethasone on the early expression of RhoA have been investigated in brains of TBI rats by immunohistochemistry. In brains of rats treated with TBI alone, significant RhoA+ cell accumulation was observed at 18 h post-injury and continuously increased during our observed time period. The accumulated RhoA+ cells were distributed to the areas of pannecrosis and selective neuronal loss. Most accumulated RhoA+ cells were identified as active microglia/macrophages by double-labelling. Dexamethasone (1 mg/kg body weight) was intraperitoneally injected on day 0 and 2 immediately following brain injury. Numbers of RhoA+ cells were significantly reduced on day 1 and 2 following administration of dexamethasone but returned to vehicle control level on day 4. However, dexamethasone treatment did not change the proportion of RhoA+ cells. These observations suggest that dexamethasone has only a transient effect on early leukocyte recruitment.
Zhang
Zhiren
Z
Institute of Brain Research, University of Tuebingen, Calwer Str. 3, 72076 Tuebingen, Germany. zhangzhiren@yahoo.com
Fauser
Uwe
U
Schluesener
Hermann J
HJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D020742:rhoA GTP-Binding Protein