Ion Homeostasis in Rat Brain in vivo: Intra- and Extracellular [Ca2+] and [H+] in the Hippocampus during Recovery from Short-Term, Transient Ischemia

Changes in intra- and extracellular [Ca 2+ ] and [H + ], together with alterations in tissue Po 2 and local blood flow, were measured in areas CA 1 and CA 3 of the hippocampus during recovery (up to 8 h) after an 8-min period of low-flow ischemia. Restoration of blood supply was followed by an immediate rise in flow and tissue Po 2 above normal, with large fluctuations in both persisting for up to 4 h. In area CA 1 , [Ca 2+ ] i decreased rapidly from an ischemic mean value of 30 μ M to a control mean level of 73.1 n M in 20–30 min, whereas normalization of [Ca 2+ ] e took ∼1 h. Recovery of [Ca 2+ ] i was accelerated by preischemic administration of a calcium antagonist, nifedipine, and a free radical scavenger, N-tert-butyl-α-phenylnitrone (PBN), but not by MK-801, a blocker of N-methyl-d-aspartate receptors. There was a secondary rise in [Ca 2+ ] i in many cells beginning ∼2 h after reperfusion. This was attenuated somewhat by PBN but not clearly influenced by either nifedipine or MK-801. Changes of [Ca 2+ ] i in area CA 3 were much smaller and slightly slower than in area CA 1 and were not affected by the drugs mentioned above. In both areas CA 1 and CA 3 , pH e and pH i fell during ischemia to an average value of 6.2, from which there was a rapid initial recovery in the first 5–10 min when blood flow was restored. Thereafter tissue pH rose slowly and did not reach control levels for ∼1 h, and in some microareas not at all. It is concluded that (a) effective mechanisms for restoring normal [Ca 2+ ] i remain intact after 8 min of low-flow ischemia; (b) in neurons of area CA 1 , some insidious change in the homeostasis of calcium triggers a secondary rise in its free cytosolic concentration, which may be causally related to activation of irreversible cell damage; and (c) the changes in [Ca 2+ ] i and [Ca 2+ ] e during and following 8 min of ischemia can be adequately accounted for by movements of a fixed pool of Ca between intra- and extracellular compartments, and possible mechanisms are discussed.