Figure 4.

Hypothermia induced by the TRPV1 agonist dihydrocapsaicin provides neuroprotection in a cerebral ischemia and reperfusion mouse model of acute ischemic stroke. Focal cerebral ischemia in mice was induced by distal middle cerebral artery occlusion for 1 h, followed by 24 h reperfusion. Dihydrocapsaicin at 1.25 mg·kg⁻¹·h⁻¹ or vehicle were infused by subcutaneously implanted osmotic pumps (∼6 μl/h) from the onset of reperfusion until 10 h after reperfusion. In the “DHC (hypothermia)” (n=8) and “Vehicle” (n=10) groups, mice were kept in a warm cage only during the first 90 min of reperfusion. In the “DHC (normothermia)” group (n=6), mice were kept in a warm cage for 10 h to avoid the temperature drop, as a control for hypothermia-independent effects of dihydrocapsaicin. (A) Core temperature of mice during the initial 4 h of reperfusion. The two dashed lines demarcate the conventional therapeutic range of hypothermia (32–34°C). (B) Representative 2,3,5-triphenyltetrazolium chloride (TTC)-stained histological brain sections, (C) fractional infarct volume, and (D) scores in a panel of behavioral tests in dihydrocapsaicin- and vehicle-treated mice at 24 h reperfusion (*P < 0.05, **P < 0.001). Adapted from Cao et al. ⁹² © The American Physiological Society. Permission to reuse must be obtained from the rightsholders.