title: Cooling produces minimal neuropathology in neocortex and hippocampus.
abstract: Cooling is a potential treatment for several neurological diseases. We have examined rodent and cat neocortex, cooled to 5 and 3 degrees C, respectively, to identify a lower limit for safely cooling brain. Rat neocortex, intermittently cooled with a thermoelectric device for 2 h, showed no signs of neuronal injury after cresyl violet or TUNEL staining. Neurons were also preserved in cat cortex cooled for up to 2 h daily for 10 months. Cooled rat and cat cortex showed glial proliferation, but this was also observed in sham-operated rat cortex. When hippocampal slices from mice expressing the Green Fluorescent Protein (GFP) in neurons were cooled to 5 degrees C, but not higher temperatures, we saw reversible dendritic beading and spine loss after 15-30 min. While there may be biochemical and functional alterations in brain cooled as low as 5 degrees C, the neuropathological consequences of brain cooling appear to be insignificant.
authors.affiliation: Department of Neurology-Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Kennedy
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Lomber
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rothman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology*; D002415:Cats; D003080:Cold Temperature / Q000009:adverse effects*; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000009:adverse effects* / Q000592:standards; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins