Mild hypothermia reduces spreading depolarizations and infarct size in a swine model

Abstract

Spreading depolarizations (SDs) have been linked to infarct volume expansion following ischemic stroke. Therapeutic hypothermia provides a neuroprotective effect after ischemic stroke. This study aimed to evaluate the effect of hypothermia on the propagation of SDs and infarct volume in an ischemic swine model. Through left orbital exenteration, middle cerebral arteries were surgically occluded (MCAo) in 16 swine. Extensive craniotomy and durotomy were performed. Six hypothermic and five normothermic animals were included in the analysis. An intracranial temperature probe was placed right frontal subdural. One hour after ischemic onset, mild hypothermia was induced and eighteen hours of electrocorticographic (ECoG) and intrinsic optical signal (IOS) recordings were acquired. Postmortem, 4 mm-thick slices were stained with 2,3,5-triphenyltetrazolium chloride to estimate the infarct volume. Compared to normothermia (36.4 ± 0.4°C), hypothermia (32.3 ± 0.2°C) significantly reduced the frequency and expansion of SDs (ECoG: 3.5 ± 2.1, 73.2 ± 5.2% vs. 1.0 ± 0.7, 41.9 ± 21.8%; IOS 3.9 ± 0.4, 87.6 ± 12.0% vs. 1.4 ± 0.7, 67.7 ± 8.3%, respectively). Further, infarct volume among hypothermic animals (23.2 ± 1.8% vs. 32.4 ± 2.5%) was significantly reduced. Therapeutic hypothermia reduces infarct volume and the frequency and expansion of SDs following cerebral ischemia.

Induction and Characterization of Spreading Depolarizations in Swine Following Superior Sagittal Sinus Occlusion: A Novel Gyrencephalic Model Study

“…The present work, however, demonstrates that SDs can be induced in the gyrencephalic brain after venous occlusion by clipping the middle third of the SSS. Still, compared to our previous experiments, where an arterial stroke model was performed by clipping the middle cerebral arteries of the swine [9][10][11]. This study found a lower SD incidence and absence of infarction formation.…”

“…Images were captured at a rate of one per second at full resolution. Post-acquisition, the images underwent an elastic transformation as part of an o ine registration process, enhancing the quality of imaging and analysis, as applied in previous studies [10,14,18]. LSCI monitoring.…”

“…In lissencephalic brains, SDs can be induced by opening the scalp and applying mechanical stimulation with a low threshold [8]. In contrast, we have previously studied SDs in the gyrencephalic swine brain under normoxic and arterial ischemic conditions [9][10][11][12][13][14] and found similarities between the swine brain and human recordings [15]. The swine's gyrencephalic brain also responds to therapy similarly to patients but in contrast to rodents, which require much higher doses of the same blocking drugs [16,17].…”

The neurophysiological effect of mild hypothermia in gyrencephalic brains submitted to ischemic stroke and spreading depolarizations

“…The animal preparation, surgical procedure, temperature measurement, and infarct volume determination are extensively explained in our article ( Kentar et al, 2023 ).…”

“…To understand the neurophysiological mechanism associated with mild hypothermia in stroke, we conducted a post hoc analysis of previously reported MCAo experiments in swine ( Kentar et al, 2023 ). We used the ECoG recording signals to monitor the power changes of the frequency bands during the infarct evolution and the development of SDs.…”