POTASSIUM CHANNELS AND CEREBRAL HEMODYNAMICS AFTER BRAIN

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Traumatic injury is the leading cause of death of infants and children and mortality is greatly increased in the presence of head injury. While the effects of brain injury have been investigated extensively in the adult, less is known about brain injury in the newborn/infant. Previous data have shown that cerebral blood fell and pial arteries constricted more in newborn vs. juvenile pigs, supporting the idea that the newborn is exquisitely sensitive to brain injury. Additionally, responses to several nitric oxide dependent dilator stimuli were either blunted or reversed to constricted following the insult. Relaxation of blood vessels can be mediated by several mechanisms, including cGMP, cAMP, and K+ channels in cerebrovascular control under physiologic conditions, less is known concerning their contributions under pathologic conditions. This proposal is based on preliminary data that dilation by endogenous and synthetic K+ channel activators are blunted after brain injury. Therefore, the hypothesis is addressed by the proposed research is that impaired K+ channel function contributes to altered cerebral hemodynamics resulting in impaired cerebrovascular function and neuronal pathology following brain injury. To address this hypothesis, three specific aims will be pursued: 1) characterize the effect of brain injury on K+ channel activity as a function of age and time, 2) determine the mechanism of altered K+ channel activity following brain injury as a function of age and time and 3) determine the functional significance of the relationship between impaired K+ channel function and altered cerebral hemodynamics following brain injury as a function of age and time. The close cranial window technique will be use din newborn and juvenile pigs to measure pial artery diameter and collect CSF for vasoactive metabolite analysis via radioimmunoassay. Histochemical and immunohistochemical indices of brain damage such as cresyl violet and microtuble associated protein 2 will be used to characterize the effects of brain injury in the newborn and juvenile pig. These studies may lead to therapies for brain injured children.