Cerebral norepinephrine depletion enhances recovery after brain ischemia.
Monoamine neurotransmitters, especially norepinephrine (NE), may have an important role in the pathophysiological aspects of postischemic cerebral dysfunction. In previous studies of post-decapitation-induced ischemia, we found that NE depletion caused a delay in glycogen breakdown but did not influence any of the other known biochemical abnormalities that accompany brain ischemia. In this study, we have turned to a model of transient incomplete and diffuse forebrain ischemia in the rat to examine the effects of cerebral NE depletion on the recovery after brain ischemia of levels of high-energy phosphate compounds, products of intermediary oxidative metabolism, and free fatty acids. We found that a unilateral lesion of the locus ceruleus and the resultant depletion of NE in the ipsilateral cerebral cortex had no effect on sham-operated controls nor on rats subjected to ischemia alone. However, in rats subjected to ischemia followed by 15 minutes of recirculation, the NE-depleted cerebral cortex had significantly higher phosphocreatine and adenosine triphosphate levels and energy charge, and lower adenosine monophosphate and docosahexaenoic acid concentrations. With longer periods of recirculation, these side-to-side differences were not apparent. These results suggest that activity of the central NE systems during transient brain ischemia has deleterious effects on the biochemical recovery of the cerebral cortex from severe ischemic insults.
D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003401:Creatine / Q000378:metabolism; D004292:Dominance, Cerebral / Q000502:physiology; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006400:Hematocrit; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D003401:Creatine; D009638:Norepinephrine