DEXAMETHASONE PREVENTS CEREBRAL INFARCTION WITHOUT AFFECTING CEREBRAL BLOOD-FLOW IN NEONATAL RATS

Background and Purpose: We recently demonstrated that pretreatment with the synthetic glucocorticoid dexamethasone prevents hypoxic-ischemic brain damage in neonatal rats. Presently, we examine whether this protective effect of dexamethasone is due to an improvement in local cerebral blood flow. Methods: Neonatal rats were treated with either vehicle or 0.1 mg/kg i.p. dexamethasone 24 hours before hypoxia-ischemia (right carotid artery occlusion+3 hours of 8% O2). Cerebral blood flow was measured with [C-14] iodoantipyrine autoradiography after either 2 (n = 17) or 3 (n = 15) hours of hypoxia-ischemia. Additional animals (n = 20) were perfusion-fixed 3 days after hypoxia-ischemia. The area of cerebral pathological changes was measured from hematoxylin and eosin-stained coronal sections taken at three different levels. Results: Pathological outcome differed between groups. In vehicle-treated rats, sections from anterior, mid, and posterior portions of the cerebrum all had extensive infarction or cellular necrosis ipsilateral to the occlusion (mean areas of damage were 62.6+/-10%, 70.2+/-9%, and 54.2+/-8%, respectively). However, in dexamethasone-treated animals, brain damage in sections at corresponding levels was minimal (0%, 1.6+/-2%, and 1.5+/-1%, respectively; p<0.0002). In contrast to the pathological results, cerebral blood flow was equivalent in the dexamethasone- and vehicle-treated groups. After either 2 or 3 hours of hypoxia, cerebral blood flow was reduced 60-80% ipsilateral to the carotid artery occlusion in animals treated with either vehicle or dexamethasone. Conclusions: Despite ischemic levels of cerebral blood How, pretreatment with dexamethasone prevents cerebral damage in neonatal rats. Instead of improving local cerebral perfusion, dexamethasone presumably acts via peripheral or central glucocorticoid receptors to produce some alteration in the brain that decreases its susceptibility to hypoxia-ischemia.