Mechanisms for anoxic survival in the vertebrate brain.
When energy supplies to the mammalian brain are significantly reduced by anoxia, for a very short time energy requirements are curtailed by such routes as the suppression of synaptic transmission, while energy supply is enhanced by an increase in cerebral blood flow and an increase in glycolysis. The reduction of ATP consumption is insufficient to match the greatly curtailed supply of ATP coming from anaerobic glycolysis and the hydrolysis of PCr, and within minutes ATP falls, there is a loss of ion homeostasis with depolarization, and cell death occurs. The anoxia-tolerant species, like the turtle, appear to employ similar mechanisms to reduce energy expenditure, but in addition to such means as increases in inhibitory neurotransmitters and the manipulation of ion channel activities, they are able to reduce the energy costs to a level that can be met by a greatly reduced supply from anaerobic glycolysis. In this way ATP levels are maintained for many hours, and anoxic depolarization, with its concomitant consequences such as an uncontrolled release of excitatory amino acids are avoided. The greater anoxic tolerance of the mammalian neonate brain is due in part to intrinsic lower metabolic requirements and, perhaps through mechanisms similar to those in the turtle, to suppress metabolic demand. Studies of the survival mechanisms of anoxia-tolerant brains of such species as the turtle and crucian carp are not only of value for investigating a remarkable neuronal adaptation, but they promise to provide a valuable model for the study of the etiology of hypoxic damage and survival strategies in the mammal.
Lutz
P L
PL
Department of Biological Sciences, Florida Atlantic University, Boca Raton 33431.
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001925:Brain Damage, Chronic / Q000209:etiology; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism; D006605:Hibernation; D006863:Hydrogen-Ion Concentration; D002534:Hypoxia, Brain / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D008322:Mammals / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D016019:Survival Analysis; D014714:Vertebrates / Q000502:physiology*
D018377:Neurotransmitter Agents; D005947:Glucose