title: The effect of blood pressure (37 vs 45 mmHg) and carotid occlusion duration (8 vs 10 min) on CA1-4 neuronal damage when using isoflurane in a global cerebral ischemia rat model.
abstract: This study presents our findings on the extent of neuronal damage in the hippocampal CA1-4 subfields following global (forebrain) cerebral ischemia in rats when using different blood pressure levels (37 vs 45 mmHg) and bilateral carotid occlusion durations (8 vs 10 min) under isoflurane anesthesia. We observed that global ischemia induced at a blood pressure of 37 mmHg resulted in high-grade CA1 neuron injury (>90%) at either duration of carotid occlusion. In contrast, global ischemia induced at a blood pressure of 45 mmHg resulted in either high-grade CA1 neuronal loss or a neuronal loss of ≈50% or less. We also noted that a post-reperfusion EEG recovery time (return of burst suppression spikes) of >12 min was associated with an 85% rate of high-grade CA1 neuronal injury. Neuronal loss in the other hippocampal subfields did not differ significantly between any of the 4 different model parameters tested. In these subfields ≈55% neuronal loss occurred in the CA2 subfield, and ≈30% in the CA3 and CA4 subfields. These findings highlight the need to assess different model parameters in order to achieve consistent high-grade CA1 neuronal damage, which, among other experimental outcomes, will improve the ability to uncover therapeutic effects using the least possible animals when assessing a neuroprotective treatment.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuro-Muscular Research Institute, Department of Neurosurgery, Sir Charles Gairdner Hospital, Western Australia, Australia. llxzhdy@sina.com
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Li
authors.forename: Kym
authors.initials: K
authors.lastname: Campbell
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002339:Carotid Arteries / Q000473:pathology; D002470:Cell Survival; D004195:Disease Models, Animal; D004569:Electroencephalography; D006624:Hippocampus / Q000166:cytology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane