title: Simple model of forebrain ischemia in mouse.
abstract: The availability of genetically engineered mice allows the unraveling of the role of specific proteins in mechanisms of ischemic brain injury. Due to the high variability of their vascular anatomy, mouse models of global cerebral ischemia are rather complex. In the present study, we describe a simple model of mouse forebrain ischemia where the bilateral common carotid artery occlusion (BCCO) is combined with isoflurane-induced hypotension. The forebrain ischemia was induced by BCCO that was preceded by increase of the isoflurane level from 1.5% to 5% in the respiratory gases. This caused a decrease of the mean arterial blood pressure (MABP) to about 30mmHg and the cerebral blood flow dropped to 5% of the control after the BCCO. During the 10min ischemic period both MABP and CBF remained stable and the reperfusion was induced by reducing the isoflurane level to 0% followed by removal of the carotid clamps. Mice were allowed 1, 2, 3 or 5 days survival followed by histologic analysis. The number of CA1 uninjured neurons was assessed utilizing a stereological approach. Neurodegeneration was observed at 2 days after the onset of reperfusion. At 3 days of recovery, about 40% of neurons survived and the cell death did not further increase at 5 days. Degenerative neurons were also detected in the striatum and sporadically in the cortex. This study demonstrates the feasibility of using the described model in mice that can be utilized to examine the effect of new neuroprotective compounds or use transgenic animals to test new hypothesis.
authors.affiliation: Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland Baltimore, 685 West Baltimore street, MSTF 534, Baltimore, MD 21201, United States.
authors.forename: Mitch
authors.initials: M
authors.lastname: Onken
authors.forename: Stephanie
authors.initials: S
authors.lastname: Berger
authors.forename: Tibor
authors.initials: T
authors.lastname: Kristian
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005452:Fluoresceins; D006973:Hypertension / Q000139:chemically induced; D007530:Isoflurane / Q000009:adverse effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000473:pathology; D009930:Organic Chemicals; D016548:Prosencephalon / Q000473:pathology* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013238:Stereotaxic Techniques
chemical_list: D018685:Anesthetics, Inhalation; D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D007530:Isoflurane