Mitochondrial response to calcium in the developing brain

Developmental differences in mitochondrial content and metabolic enzyme activities have been defined, but less is understood about the responses of brain mitochondria to stressful stimuli during development. Cerebral mitochondrial response to high Ca²⁺ loads after brain injury is a critical determinant of neuronal outcome. Brain mitochondria isolated from 16-18-day-old rats had lower maximal, respiration-dependent Ca²⁺ uptake capacity than brain mitochondria isolated from adult rats in the presence of ATP at both a pH of 7.0 and 6.5. However, in the absence of ATP, immature brain mitochondria exhibited greater Ca²⁺ uptake capacity at pH 7.0 and 6.5, indicating a greater resistance of immature brain mitochondria to Ca²⁺-induced dysfunction under conditions relevant to those that exist during acute ischemic and traumatic brain injury. Acidosis reduced the maximal Ca²⁺ uptake capacity in both immature and adult brain mitochondria. Cytochrome c was released from both immature and adult brain mitochondria in response to Ca²⁺ exposure, but was not affected by cyclosporin A, an inhibitor of the mitochondrial membrane permeability transition. Developmental changes in mitochondrial response to Ca²⁺ loads may have important implications in the pathobiology of brain injury to the developing brain.