HYPOXIA OF BRAIN TISSUE SLICES

描述（申请人摘要）：氧气供应中断是

DESCRIPTION (Applicant's Abstract): Interrupted supply of oxygen is the main cause of neuron injury in cerebral stroke and transient cerebral ischemia. The long-range goal of this project is a comprehensive study of the acute effects of hypoxia on central nervous tissue of mammals. Hypoxic failure of cerebral function takes place in a succession of ell defined stages. First synaptic transmission is depressed, then cells lose membrane potential, release much of their potassium and take up sodium, chloride, calcium and water. Timely reoxygenation is still followed by recovery of neuron function, but if the depolarized state continues too long, injury becomes irreversible. In the past this laboratory has contributed to the understanding of each of these hypoxic changes. The goal for the present application is the biophysical mechanism of the hypoxic depolarization. Several hypotheses are proposed to explain the increased permeability of the neuronal membranes that result in the profound depolarization and transmembrane ion exchanges. The validity of these proposals will be tested with a variety techniques, including: Recording of ion changes in interstitial space of cerebral tissue slices; whole-cell recordings from neurons in brain tissue slices; single-channel recording from cell-attached patches; imaging of the intrinsic optical changes of cerebral tissue during hypoxia; confocal fluorescence microscopic imaging of intracellular calcium activity of cells in tissue slices. Besides neurons, the role of glial cells will also be studied.