Use of adrenocorticotrophic hormone analog to minimize brain injury

STUDY OBJECTIVES: 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. SETTING AND DESIGN: 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. SUBJECTS: 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). INTERVENTIONS: Post-traumatic subcutaneous administration of nanomolar concentrations of GMM2 (31 nmol per rat). MEASUREMENTS AND MAIN 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. CONCLUSION: 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.