Use of adrenocorticotrophic hormone analog to minimize brain injury.
OBJECTIVE
To investigate the effects of a vasoactive analog of adrenocorticotrophic hormone (GMM2) on time-dependent disturbances in regional cerebral blood flow, permeability-capillary surface area products, and intracranial pressure in a rat model of moderate concussion/brain injury.


METHODS
Regional permeability-capillary surface area products and cerebral blood flow were measured at two hours after trauma. Intracranial pressure was monitored for 120 hours after trauma.


METHODS
Male Wistar rats (330 to 430 g) (regional cerebral blood flow studies, n = 35; permeability-capillary surface area product studies, n = 36; intracranial pressure studies, n = 32).


METHODS
Post-traumatic subcutaneous administration of nanomolar concentrations of GMM2 (31 nmol per rat).


RESULTS
Untreated trauma acutely increased average brain permeability-capillary surface area products for sucrose and decreased average brain cerebral blood flow. Moreover, it produced marked and prolonged increases in intracranial pressure. Post-traumatic subcutaneous administration of nanomolar concentrations of GMM2 effectively reduced the early hypoperfusion, blood-brain barrier leakiness, and pathologic elevation of intracranial pressure.


CONCLUSIONS
Post-traumatic administration of GMM2, in nanomolar amounts, can prevent or reverse significantly the serious cerebrovascular sequelae of moderate head injury in this animal model. In view of its potency, low toxicity, and other neuroprotective properties, in both rats and human beings, these data suggest that GMM2 may have considerable clinical benefits in the treatment of central nervous system trauma.
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan.
H
H
Goldman
M
M
Morehead
S
S
Murphy
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D009479:Neuropeptides; D000324:Adrenocorticotropic Hormone