Article
The effect of moderate hypothermia on spreading depolarization after middle cerebral artery occlusion in a swine model
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Published: | June 18, 2018 |
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Objective: Spreading depolarizations (SDs) have been reported in many animal stroke models that arises from the core of the ischemic area and spreads across the penumbra and occurs in chiefly in ischemic stroke patients. Hypothermia is a promising neuroprotective strategy that has been studied in running clinical trials. The mechanisms to produce neuroprotection are not completely understood. The effect of hypothermia on spreading depolarization (SD) in gyrencephalic brain is not known. Our goal was to establish a permanent middle cerebral artery occlusion (MCAO) model through the transorbital approach in order to produce focal cerebral ischemia in swine. Through a bilateral craniectomy, intrinsic optical signal imaging (IOS) and electrocorticography (ECoG) were used to study the cortical spreading depressions and characterize its hemodynamic and electrical changes in normothermia and hypothermia.
Methods: Thirty-nine animals in five groups were used in this study. Group 1: Ten animals to establish the MCAo model. Group 2: Sham group as a control group for physiological variables performing only bilateral craniectomy without MCAO (n=9). Group 3: Bilateral craniectomy and MCAo (n=10). In a second phase two groups were randomly assigned to either normothermia (36,5°-37,5°) (Group4, n=5) or moderate hypothermia (32°-33°) (Group 5, n=5). The incidence, amplitude, duration and expansion of SD were studied.
Results: We confirm the reliability of performing live monitoring in cerebral infarctions using our MCAo protocol over long periods of time experiments. SD were observed in all groups after MCAo. Our results show that incidence of SD is reduced by moderate hypothermia (mean number of SD per hour in hypothermia vs. control in IOS: 1.28 ± 1.16 vs. 3.5 ± 1.63, p < 0.05, and in ECoG: 0.87 ±1.09 vs. 2.88 ± 2.24, p < 0.05), while the electrical and hemodynamic characteristics were not affected.
Conclusion: SDs were observed using live monitoring of ECoG and iOS after MCAO in a swine model. Our observation is that hypothermia is highly effective in reducing the incidence of SD in gyrencephalic brain. This unknown mechanism of neuroprotection in hypothermia could be used to support other therapeutic strategies.