Effects of Temperature on Evoked Electrical Activity and Anoxic Injury in CNS White Matter

Abstract

Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42°C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to 37°C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37°C was 35.4 ± 7%; when the temperature was lowered by 2.5°C (i.e., to 34.5°C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 ± 15% ( p < 0.00001). Lowering the temperature to 32°C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 ± 14% of the control CAP area). Conversely, if temperature was increased to >37°C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42°C was 8.5 ± 7% ( p < 0.00001). Hypothermia (i.e., 32°C) for 30 min immediately following anoxia at 37°C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O₂ consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990 a). It is more likely that temperature affects the rate of ion transport by the Na⁺–Ca²⁺ exchanger, the transporter responsible for intracellular Ca²⁺ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca²⁺.