THE EFFECT OF THE ADRENOCORTICAL AXIS UPON RECOVERY FROM CLOSED-HEAD INJURY

Fragments and analogs of the hormone ACTH were previously shown to hav e beneficial effect on the outcome of head injury, while elevated leve ls of corticosterone (CS) exacerbate it, In the present study we inves tigated the role of the hypothalamo-pituitary-adrenal (HPA) axis in th e pathophysiology of closed head injury (CHI), CHI was produced in eth er-anesthetized rats by a calibrated weight-drop device, After evaluat ing the functional status according to a set of criteria, at 1 and 24 h, the rats were sacrificed and cortical tissue was removed to determi ne its water content, CHI was also produced in rats that underwent sur gical procedures to remove their adrenal gland (ADEX) or the pituitary (HypoX), thus altering the levels of their circulating HPA hormones, Given after CHI, to rats with intact HPA axis, ACTH reduced edema and improved recovery, ADEX rats (6 days postsurgery) had 10-fold higher l evels of plasma ACTH, ADEX rats subjected to CHI showed improved funct ional outcome (p = 0.008) and reduced edema (p = 0.02), We then produc ed CHI in three groups of rats: HypoX (15 days postsurgery), HypoX tre ated with ACTH, and controls, In HypoX rats, CHI resulted in increased mortality (35% vs 0) and edema in the surviving rats, and a slower re covery, as compared with the control, Mortality was prevented, edema s lightly reduced, and recovery significantly improved after administrat ion of 1-24-ACTH to HypoX rats with CHI, Our results suggest that ACTH has a cerebroprotective effect on the outcome of CHI.