Permeability of the blood-brain barrier to calcium in adrenal insufficiency

Abstract

Experiments purporting to prove a marked breakdown of the blood-cerebrospinal fluid barrier to calcium ions in the absence of glucocorticoids have been reported in the literature4, 5. The phenomenon, if confirmed, would be of considerable fundamental and applied significance. It would imply that this usually tight barrier was dependent on endocrine activity. Further, it would suggest a mechanism for the known action of glucocorticoids in reducing cerebral oedema. We have studied the permeability of both the blood-brain and blood-cerebrospinal fluid barriers to calcium with the view of confirming this observation. In the rat, both at normal and elevated plasma calcium levels, we have been unable to find evidence in support of this finding. Similarly, in the lightly anaesthetised adrenalectomised rabbit, no increase in cerebrospinal fluid calcium was seen during acute hypercalcaemia. Male CSE-Wistar rats weighing approximately 350 g were adrenalectomised by the lumbar approach under ether anaesthesia. The animals were allowed to recover and were maintained on small animal diet with 0.9 ~o saline as drinking water ad libitum for a minimum of 8 days before infusions were carried out. In the rat maintained on saline, the cardiovascular system has returned to normal 8 days after adrenalectomy 6. Solutions were infused into the femoral vein of rats anaesthetised with intraperitoneal Nembutal (6 mg/100 g body weight; 4.5 mg/100 g in adrenalectomised animals). Intact controls and adrenalectomised animals were perfused in parallel. Infusion schedules were devised to maintain constant blood levels of either calcium-45 or of raised total calcium. Blood levels were monitored by sampling from the cannulated femoral artery on the same side. The effectiveness of the adrenalectomy was confirmed by corticosterone analysis on the last sample of blood taken from the surgically stressed animal. Corticosterone was estimated fluorimetrically by a modification of the Zenker-Bernstein method s. For studies at normal plasma levels, 45Ca as a calculated amount of radioisotope in a total calcium concentration of 5 mg/100 ml was infused with a Har-