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), pp. 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
Digital Object Identifier (DOI): doi:10.1111/j.1471-4159.2004.02711.x
ISSNs: 0022-3042 (print)
Keywords: cerebral ischaemia, free radical, hypothermia, neuroprotection, nitric oxide.
Subjects:
ePrint ID: 24087
Date :
Date Event
2004Published
Date Deposited: 22 Mar 2006
Last Modified: 16 Apr 2017 22:42
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/24087

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