A New Mouse Model of Global Brain Ischemia
Field:	Disorders of the nervous system
Authors:	Olsson, Tomas Smith, Maj-Lis Wieloch, Tadeusz
Address of presenting author:	Experimental Brain Research Wallenberg Neuroscience Center 221 85 LUND, Sweden
E-mail:	tomas.olsson@expbr.lu.se
Phone:	046-2220609
Fax:	046-2220615
Text of abstract:	The purpose of this work was to develop a mouse model for global ischemia, not too complicated, but still with monitoring of all important parameters. A model of transient global brain ischemia, induced with bilateral carotid occlusion, in male C 57 Black mice is described, where the mortality is low and reproducibility good. Animals were anesthetised with 1% halothane in 70% N2O and 30% O2, intubated and connected to a ventilator and given muscle relaxant. After bilateral carotid artery clamping, laser doppler flowmetry was used to confirm the reduction in cerebral blood flow (CBF) in parietal cortex on occlusion. A closed box over the upper part of the body with a flow of humidified warm air were used to maintain head temperature at 37.1 ± 0.3°C. Rectal temperature was strictly kept at 37.0 to 37,5°C by a feedback homeothermic blanket during ischemia. After ischemia the animals were kept for 24h in an incubator with a temperature of 34 - 35°C. The animals were perfusion fixed 7 days after ischemia and the brains were processed for histological evaluation with light microscopy. Experiments with different ischemic time duration (6, 8, 10, 12, 15 or 20 min) showed that 10 min ischemia or less did not generate reproducible damage, and when the duration was 15 min or more the animal died before fixation, usually the first day. 12 min ischemia induced reproducible damage in CA1 and CA2 subfields of hippocampus, layers 2 and 3 in cortex, striatum and sometimes in the ventroposterior nuclei of thalamus. Only animals that dropped to under 10% of normal CBF upon occlusion were included in the study. Brain temperature during ischemia as well as the body temperature during the first 24h were very critical for the development of brain damage. Body temperatures under 35°C prevented brain injury, while temperatures over 39°C during the first 24h often resulted in death before fixation the 7th day or in very severe brain damage. This model seems to be a reliable model, and give new possibilities to investigate interesting genes and their role in neuronal death, and may contribute to develop new therapies against stroke.
Keywords:	Ischemia, Mouse, Hippocampus, Neuronal death, Model

Created 20000-05-09