The effect of the adrenocortical axis upon recovery from closed head injury

Fragments and analogs of the hormone ACTH were previously shown to have beneficial effect on the outcome of head injury, while elevated levels of corticosterone (CS) exacerbate it. In the present study we investigated the role of the hypothalamo-pituitary-adrenal (HPA) axis in the pathophysiology of closed head injury (CHI). CHI was produced in ether-anesthetized rats by a calibrated weight-drop device. After evaluating the functional status according to a set of criteria, at 1 and 24 h, the rats were sacrificed and cortical tissue was removed to determine its water content. CHI was also produced in rats that underwent surgical 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 levels of plasma ACTH. ADEX rats subjected to CHI showed improved functional outcome (p = 0.008) and reduced edema (p = 0.02). We then produced CHI in three groups of rats: HypoX (15 days postsurgery), HypoX treated with ACTH, and controls. In HypoX rats, CHI resulted in increased mortality (35% vs 0) and edema in the surviving rats, and a slower recovery, as compared with the control. Mortality was prevented, edema slightly reduced, and recovery significantly improved after administration of 1-24-ACTH to HypoX rats with CHI. Our results suggest that ACTH has a cerebroprotective effect on the outcome of CHI.