Cyclic AMP Concentrations in Rat Neocortex and Hippocampus During and Following Incomplete Ischemia: Effects of Central Noradrenergic Neurons, Prostaglandins, and Adenosine

Abstract

The concentrations of cAMP, noradrenaline [norepinephrine], glycogen, glucose, lactate, pyruvate, labile phosphate compounds and free fatty acids were investigated in the rat neocortex and hippocampus during and following cerebral ischemia. An incomplete ischemia of 5 and 15 min duration was induced by bilateral carotid clamping combined with hypotension. The postischemic events were studied after 5, 15 and 60 min of recirculation. Five minutes of ischemia did not significantly alter the neocortical or hippocampal concentrations of cAMP. After 15 min of ischemia the neocortical levels decreased significantly below control values. In the recirculation period following ischemia a significant elevation of the cAMP concentrations was observed. Following 5 min of recirculation after 5 min of ischemia the levels increased from 2.53 .+-. 0.21 nmol/g to 5.18 .+-. 0.09 nmol/g in the neocortex and from 2.14 .+-. 0.16 nmol/g to 3.52 .+-. 0.35 nmol/g in the hippocampus. Five minutes of recirculation following 15 min of ischemia led to a significant increase in the levels of cAMP, to 12.86 .+-. 1.43 nmol/g in the neocortex to 5.58 .+-. 0.57 nmol/g in the hippocampus. With longer recirculation periods the cAMP levels progressively decreased and were similar to control values after 60 min. Depletion of cortical noradrenaline by at least 95% was performed by injections of 6-hydroxydopamine into the ascending axon bundles from the locus ceruleus. The lesion did not significantly change the ischemic or postischemic neocortical and hippocampal levels of cAMP, glycogen or free fatty acids including arachidonic acid. Treatment of the animals with theophyllamine (23, 46, and 92 mg/kg) or indomethacin (10 mg/kg) did not affect the postischemic levels of cAMP. Apparently, central noradrenergic neurons, prostaglandins and adenosine are not of major importance for the observed postischemic elevations of cAMP and the changes in the concentrations of free fatty acids measured during and following ischemia are not mediated by noradrenergic neurons.