Intraischaemic hypothermia reduces free radical production and protects against ischaemic insults in cultured hippocampal slices


McManus, Terence, Sadgrove, Matthew, Pringle, Ashley K., Chad, John E and Sundstrom, Lars E. (2004) Intraischaemic hypothermia reduces free radical production and protects against ischaemic insults in cultured hippocampal slices. Journal of Neurochemistry, 91, (2), 327-336. (doi:10.1111/j.1471-4159.2004.02711.x).

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Description/Abstract

Hypothermia has been demonstrated to be an effective neuroprotective
strategy in a number of models of ischaemic and
excitotoxic neurodegeneration in vitro and in vivo. Reduced
glutamate release and free radical production have been
postulated as potential mechanisms underlying this effect but
no definitive mechanism has yet been reported. In the current
study, we have used oxygen–glucose deprivation in organotypic
hippocampal slice cultures as an in vitro model of cerebral
ischaemia. When assessed by propidium iodide
fluorescence, reducing the temperature during oxygen–glucose
deprivation to 31–33C was significantly neuroprotective
but this effect was lost if the initiation of hypothermia was
delayed until the post-insult recovery period. The neuroprotective
effects of hypothermia were associated with a significant
decrease in both nitric oxide production, as assessed
by 3-amino-4-aminomethyl-2¢,7¢-difluorofluorescein fluorescence,
and superoxide formation. Further, hypothermia significantly
attenuated NMDA-induced nitric oxide formation in
the absence of hypoxia/hypoglycaemia. We conclude that the
neuroprotective effects of hypothermia are mediated through
a reduction in nitric oxide and superoxide formation and that
this effect is likely to be downstream of NMDA receptor activation.

Item Type: Article
ISSNs: 0022-3042 (print)
Related URLs:
Keywords: cerebral ischaemia, free radical, hypothermia, neuroprotection, nitric oxide.
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 24087
Date Deposited: 22 Mar 2006
Last Modified: 27 Mar 2014 18:13
URI: http://eprints.soton.ac.uk/id/eprint/24087

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