gms | German Medical Science

Objective: Peri-infarct Depolarizations (PIDs) are a type of spreading Depolarization (SD) that has been linked to infarct volume expansion following an ischemic stroke. Therapeutic hypothermia has been found to provide a neuroprotective effect after an ischemic stroke and may improve outcomes. Therefore, in this study, we aimed to evaluate the effect of hypothermia on the propagation of PIDs and infarct volume expansion in a swine model of focal cerebral ischemia.

Methods: Through a left orbital exenteration, the middle cerebral arteries (MCAs) were identified and surgically clipped (MCAo) in 12 German Landrace swine weighing 28-32 kg. Extensive bilateral upper craniotomy and durotomy were performed and two 5-contact electrocardiographic (EcoG) recording strips were placed bilaterally over the parietal and frontal cortex. An intracranial temperature probe was placed over the right frontal lobe under the dura mater to measure directly cortical temperature. One hour after the onset of ischemia, mild hypothermia was induced in half of the swine, reducing the temperature at an interval of 2°C/hour until reaching 32°C. After the MCAo, ECoG, and Intrinsic Optical Signal (IOS) recordings were performed. Postmortem 4mm-thick-slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC) in order to estimate the infarct volume.

Results: When compared to the normothermic group, a significant reductive effect of hypothermia on the number and expansion of SDs was detected in both ECoG (normothermic: 3.5 ± 2.1 SDs/hour; expansion of 73.2 ± 5.2% vs. hypothermic: 1.0 ± 0.7 SDs/hour; expansion of 41.9 ± 21.8%) and IOS recordings (normothermic: 3.9 ± 0.4 SDs/hour; expansion of 87.6 ± 12.0% vs. hypothermic: 1.4 ± 0.7 SDs/hour; expansion of 67.7 ± 8.3%) (Figure 1 [Fig. 1]). In terms of infarct volume, we found a significant difference between the normothermic (9.0 ± 0.8 cm3) and hypothermic (6.0 ± 1.0 cm3) groups, indicating an important reduction of the infarction in the animals that underwent hypothermia (Figure 2 [Fig. 2]).

Conclusion: Therapeutic hypothermia was successful in reducing the incidence and expansion of SDs following cerebral ischemia, as showed by ECoG and IOS recordings, and in the reduction of the infarct volume, as evaluated by postmortem staining.