An ACTH analog minimizes cerebrovascular damage in an animal model of moderate brain injury.
An ACTH1-14-related analog (GMM2) was tested for efficacy in reducing the cerebrovascular pathology that follows moderate, closed-head injury in our rat model. Posttraumatic subcutaneous administration of nanomolar amounts of GMM2 significantly minimized both the hypoperfusion and the increased blood-brain permeability observed 2 h following a concussion. Posttraumatic administration of the peptide also reduced the elevated brain water content observed at 24 and 48 h postinjury to nonsignificant levels. These findings complement previously described observations that GMM2 treatment prevents dangerous elevations of ICP (> 25 mm Hg) at 24 to 72 h in this model of head injury. In view of the potency and low toxicity of GMM2 these observation suggest that the peptide may have considerable clinical application in interrupting pathologic sequelae of traumatic brain injury.
Goldman
H
H
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Morehead
M
M
Murphy
S
S
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
C086612:GMM2; D009479:Neuropeptides