Intracellular calcium accumulation during the evolution of hypoxic-ischemic brain damage in the immature rat

An excessive intracellular accumulation of calcium (Ca2+) in neurons and gl ia has been proposed to represent a major 'final common pathway' for cell d eath arising from hypoxia-ischemia. To clarify the role of altered calcium flux into the perinatal brain undergoing hypoxic-ischemic damage, 7-day pos tnatal rats underwent unilateral common carotid artery ligation followed by systemic hypoxia with 8% oxygen. This insult is known to produce brain dam age in the form of selective neuronal death or infarction largely limited t o the cerebral hemisphere ipsilateral to the arterial occlusion. Either pri or to or following hypoxia-ischemia, the rat pups received a s.c. injection of (CaCl2)-Ca-45, and specimens of blood, cerebrospinal fluid (CSF), and b rain were obtained for isotopic measurements and the calculation of the ext ent of brain intracellular radioactivity. During hypoxia-ischemia, there wa s a modest increase in intracellular Ca2+ radioactivity (+28-47%) in both c erebral hemispheres only after 2 h of hypoxia-ischemia. During recovery fro m 2 h of hypoxia-ischemia, intracellular Ca2+ accumulated progressively onl y in the ipsilateral cerebral hemisphere for up to 24 h, during which inter val intracellular Ca2+ decreased in the contralateral hemisphere. No such p rogressive accumulation was noted during recovery in animals previously exp osed to only I h of hypoxia-ischemia. The results suggest that a disruption of intracellular Ca2+ homeostasis is a major contributing factor in the ev olution of perinatal hypoxic-ischemic brain damage. Ca2+ accumulation is a relatively modest and late event during the hypoxic-ischemic phase, and a p rogressive overload occurs during the recovery phase only if infarction occ urs. The question remains as to whether or not the intracellular Ca2+ overl oad occurring during recovery is a contributor to or a consequence of the u ltimate brain damage. (C) 2001 Elsevier Science B.V. All rights reserved.