An ACTH Analog Minimizes Cerebrovascular Damage in an Animal Model of Moderate Brain Injury

Abstract

An ACTH_1–14-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.