title: Protection against CNS ischemia by temporary interruption of function-related processes of neurons.
abstract: 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.
authors.affiliation: Neurosurgical Service, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ames
authors.forename: K I
authors.initials: KI
authors.lastname: Maynard
authors.forename: S
authors.initials: S
authors.lastname: Kaplan
mesh_terms: 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
chemical_list: D018696:Neuroprotective Agents