Brain damage in a mouse model of global cerebral ischemia
Abstract
The importance of particular genes in neuronal death following global cerebral ischemia can readily be studied in genetically modified mice provided a reliable model of ischemia is available. For that purpose, we developed a mouse model of global cerebral ischemia that induces consistent damage to different regions of the brain and with a low mortality rate. Twelve minutes of ischemia was induced in C57BL/6 mice by bilateral common carotid artery occlusion under halothane anesthesia and artificial ventilation. Body and brain temperature were monitored and cortical cerebral blood flow in each hemisphere was measured by laser Doppler flowmeter before, during, and for 5 min after ischemia. Extensive damage was found in the striatum and marked cell damage was observed in the CA1 and CA2 regions of hippocampus and in thalamus. Mild damage was seen in the CA3 region, dentate gyrus and cortex. Hippocampal damage in the CA1 region is delayed and developed over 48 h. Intraischemic hypothermia of 33 degrees C provided a robust neuroprotection. The non-competitive N-methyl-D-aspartate receptor blocker, MK-801, did not provide protection in the hippocampus, cortex, striatum or thalamus when administered 30 min prior to ischemia or 2 h after the end of ischemia, but selectively mitigated damage in the hippocampus, when administered immediately following ischemia. This model of global cerebral ischemia may be useful in pharmacological and genomic studies of ischemic brain damage.
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In vivo rodent global ischemia data and human clinical stroke trials have been unable to indicate a clear causal role of NMDA receptors under the conditions in which receptor antagonists were applied.
“However, in vivo rodent global ischemia data (Corbett et al., 1990;Diemer et al., 1992;Olsson et al., 2003), as well as human clinical stroke trials (Lee et al., 1999;Hoyte et al., 2004;Simon, 2006) have been unable to indicate a clear causal role of these receptors under the conditions in which receptor antagonists were applied.”
From Two-Photon Imaging of Stroke Onset<i>In Vivo</i>Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines (2008) · cites this paper as Olsson et al., 2003
Studies have demonstrated delayed loss of C57BL/6 mouse cortical neurons caused by brief global ischemia using similar models.
“However, studies have also demonstrated delayed loss of C57BL/6 mouse cortical neurons caused by brief global ischemia using similar models (Olsson et al., 2003;Yonekura et al., 2004).”
From Two-Photon Imaging of Stroke Onset<i>In Vivo</i>Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines (2008) · cites this paper as Olsson et al., 2003
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Burguillos, M. A., Svensson, M., Schulte, T., Boza-Serrano, A., Garcia-Quintanilla, A., Kavanagh, E., Santiago, M., Viceconte, N., Oliva-Martin, M. J., Osman, A. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.012 · Cited by 365 · see citing works
Murphy, T. H., Li, P., Betts, K., & Liu, R. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5128-07.2008 · Cited by 261 · see citing works
“However, in vivo rodent global ischemia data (Corbett et al., 1990; Diemer et al., 1992; Olsson et al., 2003), as well as human clinical stroke trials (Lee et al.”
BackgroundChen, Z., Mao, X., Liu, A., Gao, X., Chen, X., Ye, M., Ye, J., Liu, P., Xu, S., Liu, J., et al. (2015) · Neurochemical Research · doi:10.1007/s11064-014-1483-z · Cited by 51 · see citing works
- Authors
- Olsson, T., Wieloch, T., & Smith, M.-L.
- Affiliations
- Lund University (SE)
- Corresponding author
- Olsson, Tomas
- ORCID
- Wieloch, Tadeusz
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 982
- Issue
- 2
- Pages
- 260-269
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1682882940
- Cited by
- 87
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Keywords
- global cerebral ischemia, mouse model, carotid artery occlusion, striatal damage, cortical blood flow, neuroprotection, MK-801, NMDA receptor, neuronal cell death
- MeSH terms
- Animals, Brain, Brain Ischemia, Cerebrovascular Circulation, Disease Models, Animal, Male, Mice, Inbred C57BL, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Mice
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