DNA damage is temperature dependent early after traumatic brain injury in rats

Michael Whalen, Minzhi Chen, Robert Clark, Kunlin Jin, Patrick Kochanek, Donald Marion, Steven Graham

Research output: Contribution to journalArticle

Abstract

Introduction: Hypothermia applied before or shortly after traumatic brain injury (TBI) attenuates while hyperthermia exacerbates neurologic damage in experimental TBI (Dietrich et al., 1996). DNA damage occurs in neurons undergoing necrosis and apoptosis after TBI (Clark et al., 1997). One mechanism by which hypothermia might mitigate neurologic injury is suppression of neuronal DNA damage. We hypothesized that neuronal DNA damage after TBI would be temperature-dependent within a clinically relevant range. Methods: Anesthetized male adult Sprague-Dawley rats were subjected to controlled cortical impact and maintained at brain temperature 32, 37, or 39°C (± 0.5°C; n=8/group) for 4 h. Rats were saline perfused and coronal (6 μm) brain sections were obtained through the center of the contusion. DNA damage was assessed using biotinylated dATP and the Klenow fragment of DNA polymerase I. DNA damage was quantified by light microscopy as the number of positively-labeled cells/100x field in cortex and hippocampal regions. Data are expressed as mean ± SEM. Results were analyzed by ANOVA and Student-Neuman-Keuls test. Results: DNA damage in cells was evident in ipsilateral cortex, dentate, and CA3 hippocampus but was rarely detected in CA1 or in the contralateral hemisphere. DNA damage was temperature-dependent in the dentate gyrus (9.8 ± 5.0 vs 31.0 ± 8.3 and 63.6 ± 18.1 cells/100x field)( 32°C vs 37°C and 39°C, respectively; p < 0.05) and CA-3 (4.1 ± 2.1 vs 13.0 ± 2.2 cells/100x field)(32°C vs. 39°C; p < 0.05), but not in CA-1 or peritrauma regions of the cortex. Conclusions: DNA damage in regions of hippocampus vulnerable to delayed neuronal death appears to be temperature-dependent early after TBI. One beneficial effect of hypothermia may be inhibition of DNA damage after TBI.

Original languageEnglish
Pages (from-to)A51
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
DOIs
StatePublished - 1999

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