TY - JOUR
T1 - DNA damage is temperature dependent early after traumatic brain injury in rats
AU - Whalen, Michael
AU - Chen, Minzhi
AU - Clark, Robert
AU - Jin, Kunlin
AU - Kochanek, Patrick
AU - Marion, Donald
AU - Graham, Steven
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750800813&partnerID=8YFLogxK
U2 - 10.1097/00003246-199901001-00084
DO - 10.1097/00003246-199901001-00084
M3 - Article
AN - SCOPUS:33750800813
SN - 0090-3493
VL - 27
SP - A51
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 1 SUPPL.
ER -