Protective Effects and Magnetic Resonance Imaging Temperature Mapping of Systemic and Focal Hypothermia in Cerebral Ischemia

Abstract

Background and Purpose-Hypothermia is potentially the most effective protective therapy for brain ischemia; however, its use is limited because of serious side effects. Although focal hypothermia (FH) has a significantly lower stress profile than systemic hypothermia (SH), its efficacy in ischemia has been poorly studied. We aimed to compare the therapeutic effects of each treatment on various short-and long-term clinically relevant end points. Methods-Sprague-Dawley rats were subjected to transient (45 minutes) occlusion of the middle cerebral artery. One hour after arterial reperfusion, animals were randomly assigned to groups for treatment with SH or FH (target temperature: 32°C) for 4 or 24 hours. Lesion volume, edema, functional recovery, and histological markers of cellular injury were evaluated for 1 month after ischemic injury. Effects of SH and FH on cerebral temperature were also analyzed for the first time by magnetic resonance thermometry, an approach that combines spectroscopy with gradient-echo-based phase mapping. Results-Both therapeutic approaches reduced ischemic lesion volume (P<0.001), although a longer FH treatment (24 hours) was required to achieve similar protective effects to those induced by 4 hours of SH. In addition, magnetic resonance thermometry demonstrated that systemic hypothermia reduced whole-brain temperature, whereas FH primarily reduced the temperature of the ischemic region. Conclusions-Focal brain hypothermia requires longer cooling periods to achieve the same protective efficacy as SH.However, FH mainly affects the ischemic region, and therefore represents a promising and nonstressful alternative to SH.

Inclusion criteria update for the rat intraluminal ischaemic model for preclinical studies

“…We have also established an arbitrary inclusion interval (between 25% and 45%) for DWI hemispheric infarct volume that could be a topic for discussion. We established this threshold based on previous studies (Argibay et al, 2017; Campos et al, 2011; Pérez-Mato et al, 2014; Vieites-Prado et al, 2016) in which the same inclusion protocol was used, and in which DWI volumes <25% during MCAo were associated with small subcortical ischaemia or no ischaemia at 24 h, and DWI volumes >45% were associated with a malignant infarct that affected all hemispheres and resulted in a high mortality rate. Finally, this study was performed in Sprague-Dawley rats because this is the most common strain used in studies on cerebral ischaemia; however, we are aware that this protocol should be validated in other strains and species of rat, as well as in a permanent MCAo model.…”

Mild hypothermia modulates the expression of nestin and caspase-3 in the sub-granular zone and improves neurological outcomes in rats with ischemic stroke

“…Until now, therapeutic hypothermia in patients with acute stroke has been applied only systematically by surface cooling, intravenous cooling, or cold saline infusions [ 27 ]. When considering the translation of this technique from an experimental situation to the clinic, there is already good evidence that MH, applied either during ischemia or during reperfusion, improves neurological function and reduces brain infarct volume; although data relating to systemic MH in MCAO/R rat models are limited [ 28 - 30 ]. Our results provide further evidence that systemic MH, started at the onset of ischemia, improves neurological function and reduces brain infarct volume in the rat MCAO/R.…”

Inclusion Criteria Update of the Intraluminal Ischemic Model in Rat for Preclinical Studies

“…We have also established an arbitrary inclusion interval between 25 and 45% for DWI hemispheric infarct volume that could be discussed. We have established this threshold because, based on previous studies (Argibay et al, 2017;Campos et al, 2011;Pérez-Mato et al, 2014;Vieites-Prado et al, 2016) where same inclusion protocol was used, we observed that DWI volumes under 25% during MCAo were associated with small subcortical ischemia or no ischemia at 24 hours, while DWI volumes above 45% were associated with malignant infarct that affected all hemisphere and caused a high rate of mortality. Therefore, based on this experience, we established this threshold for DWI.…”