Protection against CNS ischemia by temporary interruption of function-related processes of neurons.
Previous studies have shown that most of the energy consumption of CNS tissue is used for processes that subserve signaling functions of the cells. Since these function-related processes are probably not essential to cell viability, blocking them reversibly with a combination of pharmacologic agents should protect cells from a reduction in energy metabolism. Preliminary experiments to test this hypothesis were performed on isolated rabbit retinas. They were maintained in a newly devised chamber that permitted continuous monitoring of electrophysiological function for > or = 8 h. Ischemia was simulated by a 6-fold reduction in both O2 and glucose. This caused a rapid (t1/2 75 s) and complete loss of the light-evoked response in the optic nerve. Untreated retinas showed full recovery after 1/2 h of deprivation, but only 50% recovery after 1 h and little or no recovery after 2 or 3 h. Retinas exposed during 3 h of deprivation to a combination of six agents that abolished electrophysiologic function and reduced glucose utilization [tetrodotoxin (TTX), 2-amino-4-phosphonobutyric acid (APB), 2-amino-5-phosphonovaleric acid (APV), amiloride, Mg2+, and Li+] showed full recovery. We conclude that reducing energy requirements by blocking functional processes can prevent ischemic damage.
Ames
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Neurosurgical Service, Massachusetts General Hospital, Boston 02114, USA.
Maynard
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Kaplan
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D000818:Animals; D002490:Central Nervous System / Q000098:blood supply* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D004734:Energy Metabolism; D005071:Evoked Potentials / Q000187:drug effects*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D018696:Neuroprotective Agents