CHANGES IN BRAIN ENERGY-METABOLISM, NEUROTRANSMITTERS, AND CHOLINE DURING AND AFTER INCOMPLETE CEREBRAL-ISCHEMIA IN SPONTANEOUSLY HYPERTENSIVE RATS

In order to investigate changes in energy metabolism, neurotransmitters, and membrane disorder accompanying incomplete cerebral ischemia, a bilateral common carotid artery occlusion model of spontaneously hypertensive rats was utilized. We measured concentrations of ATP, phosphocreatine (PCr), lactate (Lac), glucose (Glu), acetylcholine (ACh), choline (Ch), and gamma-aminobutyric acid (GABA) in both the cerebral cortex and the subcortical regions after 1 h ischemia, 2 h ischemia, and 2 h reflow following 2 h ischemia, and then examined changes in concentrations of these substances during and after incomplete cerebral ischemia. Also examined were interrelations of changes in these substance levels during ischemia. In the cerebral cortex, levels of ATP, PCr, Glu, and ACh decreased, and levels of Lac, Ch, and GABA increased during ischemia. After recirculation, levels of ATP, PCr, Ch, and GABA tended to return to the normal range. On the other hand, the Lac level remained in the ischemic range and the Glu level rose and greatly exceeded the normal range. With regard to ACh, most animals showed normal levels but some exceeded the normal range. Changes in the subcortical regions were qualitatively the same as those in the cerebral cortex during and after ischemia (except with Glu), but only smaller in degrees. Glu levels remained unchanged during ischemia. Correlation of the levels of these substances in the cerebral cortex was examined using normal and ischemic values. A high correlation was generally observed between ATP and other substance levels. The relations between ATP and either PCr or Glu levels were linear. The relation between ATP and ACh levels was logarithmic. The relations between ATP and either Lac, Ch, or GABA levels were exponential. Namely, ACh, Lac, Ch, and GABA levels stayed constant until ATP fell to some fixed low level, suggesting the existence of a threshold. High correlations were also observed among Lac, Ch, and GABA levels.