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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).

Record type: Article


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.

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Published date: 2004
Keywords: cerebral ischaemia, free radical, hypothermia, neuroprotection, nitric oxide.


Local EPrints ID: 24087
ISSN: 0022-3042
PURE UUID: c37cad3b-f32d-4360-a02d-360ad6698fa8
ORCID for Ashley K. Pringle: ORCID iD
ORCID for John E Chad: ORCID iD

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Date deposited: 22 Mar 2006
Last modified: 17 Jul 2017 16:15

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Author: Terence McManus
Author: Matthew Sadgrove
Author: John E Chad ORCID iD
Author: Lars E. Sundstrom

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