Neurotoxic zinc translocation into hippocampal neurons is inhibited by hypothermia and is aggravated by hyperthermia after traumatic brain injury in rats.

摘要

Hypothermia reduces excitotoxic neuronal damage after seizures, cerebral ischemia and traumatic brain injury (TBI), while hyperthermia exacerbates damage from these insults. Presynaptic release of ionic zinc (Zn(2 +)), translocation and accumulation of Zn(2 +) ions in postsynaptic neurons are important mechanisms of excitotoxic neuronal injury. We hypothesized that temperature-dependent modulation of excitotoxicity is mediated in part by temperature-dependent changes in the synaptic release and translocation of Zn(2 +). In the present studies, we used autometallographic (AMG) and fluorescent imaging of N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining to quantify the influence of temperature on translocation of Zn(2 +) into hippocampal neurons in adult rats after weight drop-induced TBI. The central finding was that TBI-induced Zn(2 +) translocation is strongly influenced by brain temperature. Vesicular Zn(2 +) release was detected by AMG staining 1 h after TBI. At 30 degrees C, hippocampus showed almost no evidence of vesicular Zn(2 +) release from presynaptic terminals; at 36.5 degrees C, the hippocampus showed around 20% to 30% presynaptic vesicular Zn(2 +) release; and at 39 degrees C vesicular Zn(2 +) release was significantly greater (40% to 60%) than at 36.5 degrees C. At 6 h after TBI, intracellular Zn(2 +) accumulation was detected by the TSQ staining method, which showed that Zn(2 +) translocation also paralleled the vesicular Zn(2 +) release. Neuronal injury, assessed by counting eosinophilic neurons, also paralleled the translocation of Zn(2 +), being minimal at 30 degrees C and maximal at 39 degrees C. We conclude that pathological Zn(2 +) translocation in brain after TBI is temperature-dependent and that hypothermic neuronal protection might be mediated in part by reduced Zn(2 +) translocation.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 161-169. doi:10.1038/sj.jcbfm.9600176; published online 29 June 2005.