Mild hypothermia reduces activated caspase-3 up to 1 week after a focal cerebral ischemia induced by endothelin-1 in rats.
Hypothermia is a promising neuroprotective therapy that has been shown to reduce apoptosis after an ischemic insult. This study evaluated the effect of mild hypothermia on activated caspase-3 up to 1 week after the induction of a stroke. Endothelin-1 (Et-1) was used to elicit transient focal cerebral ischemia in rats. Twenty minutes after the ischemic insult, a state of mild hypothermia (33°C) was imposed for a duration of 2h. The functional outcome, infarct volume and activated caspase-3 immunoreactivity (IR) were assessed at 8, 24 and 72h, and one week after the insult. During the experiment the cerebral blood flow (CBF) was measured via Laser Doppler Flowmetry. Hypothermia improved the neurological outcome at all of the time points studied compared to the normothermic group, and was associated with a reduction in infarct volume. In both groups, activated caspase-3 IR peaked 24h after the Et-1 induced insult and hypothermia significantly reduced the number of apoptotic cells at 8h, 24h and 1 week after ischemia. Furthermore, the hypothermic treatment did not affect the CBF in the Et-1 model. These findings indicate that in the Et-1 model, hypothermia exerts a long lasting effect on stroke-induced apoptosis.
Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Tine.Zgavc@vub.ac.be
Tine
T
Zgavc
Deborah
D
De Geyter
An-Gaëlle
AG
Ceulemans
Wendy
W
Stoop
Said
S
Hachimi-Idrissi
Yvette
Y
Michotte
Sophie
S
Sarre
Ron
R
Kooijman
D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1; D007036:Hypothermia, Induced; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology
D019332:Endothelin-1; D053148:Caspase 3