Time course of acute neuroprotective effects of lithium carbonate evaluated by brain impedanciometry in the global ischemia model

Abstract

It is well known that chronic treatment with lithium gives cytoprotection from ischemia and neurodegeneration. Despite the clinical relevance, the potential effects of acute lithium treatment just before and during early stages of ischemia are not well known. Brain impedance was measured in an experimental global ischemia model, to determine these potential effects and their time course,as measured in minutes. Thiobarbital anesthetized (60 mg·kg(-1), intraperitoneal injection) male Sprague-Dawley rats were infused intravenously (i.v.) with isovolumetric amounts of ringer (n = 10 rats) or lithium (Li(2)CO(3); 10; 30; 100 mg·kg(-1); n = 6 rats per dose tested). Cortico-subcortical impedance was recorded before (20 min) and after (20 min) the infusion, and during global cerebral ischemia (20 min) induced by cardiopulmonary arrest due to the administration of D-tubocurarine. Lithium did not change tissue impedance in normoxid animals. In the ringer-infused group, global cerebral ischemia first (9 min) shows a fast voltage decay rate (-7.08%·min(-1)), followed by a slow one (-0.94%·min(-1)) for the last 11 min of the recording. Lithium, at any dose tested, induced a strong reduction in voltage decay for both fast (-3.7%·min(-1)) and slow (-5.2%·min(-1)) phases, although the reduction was more intense in the first phase (>58%, Mann-Whitney Z = 2.02; P < 0.043). The reduction was more effective at 10 mg (Li₂CO₃)·kg(-1) than at 30 or 100 mg·kg(-1). The time course of brain edema was defined by curve fitting for ringer- (time constant λ = 512.9 s) or lithium-infused animals (λ = 302.0 s). These results suggest that acute lithium infusion 20 min prior to global ischemia, strongly reduces cerebral impedance by reducing the decay rate and the duration of the fast decay phase, and increasing time constant decay during ischemia.

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