Calcium Accumulation during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat

Abstract

Summary: An excessive accumulation of calcium in neu ronal and other tissues has been postulated to represent a "final common pathway" for cell death arising from hyp oxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain under going hypoxic-ischemic injury, 7-day postnatal rats un derwent unilateral common carotid artery ligation fol lowed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in >90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]CI2, and their brains were subjected to 45Ca autora diography at 0-1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilat eral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerePerinatal cerebral hypoxic-ischemic brain damage is characterized either by selective necrosis of vulnerable neurons or infarction (Rorke, 1982;Vannucci, 1985; Volpe, 1987). Regions of immature brain especially sensitive to hypoxic-ischemic in jury include the cerebral cortex, hippocampus, striatum, and thalamus as well as selected struc tures of the brainstem. Subcortical and periventri cular white matter also is vulnerable, especially in the premature infant. The severity and distribution of the neuropathologic lesions are dependent on several factors, including the nature and duration of the insult, the gestational age of the fetus or new- 834bral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer ap parent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hyp oxic-ischemic injury. Thus, hypoxia-ischemia is asso ciated with enhanced calcium uptake into the immature brain, which does not dissipate but rather progressively accumulates for up to 15 days of recovery. The findings implicate a disruption of intracellular calcium homeo stasis as a major factor in the evolution of perinatal hyp oxic-ischemic brain damage. Key Words: Calcium Perinatal-Hypoxia-ischemia-Brain damage.born infant, and the presence or absence of super imposed systemic stress, e. g. , hypoglycemia, sepsis, or undernutrition (Vannucci and Plum, 1975). Vascular and metabolic factors (intrinsic vul nerability) also play a critical role as is known to exist in adults (Brierley and Graham, 1984).The underlying pathogenetic mechanism(s) re sponsible for the brain damaging...

Hemodynamic response to burst-suppressed and discontinuous electroencephalography activity in infants with hypoxic ischemic encephalopathy

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Regional Cerebral Glucose Utilization in the Immature Rat: Effect of Hypoxia-Ischemia

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Age-related differences in recovery of blood flow and metabolism after cerebral ischemia in swine.

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