Extraluminal Cooling of Bilateral Common Carotid Arteries as a Method to Achieve Selective Brain Cooling for Neuroprotection

Abstract

Systemic cooling to achieve brain hypothermia has been investigated as a neuroprotective therapy but can present serious adverse effects. Here we describe a novel method to selectively cool the rat brain and investigate its neuroprotective effects following transient middle cerebral artery occlusion (MCAo). The novelty of our method of selective brain cooling (SBC) was that the extraluminal cooling of the carotid arterial blood was achieved by using a cooling cuff wrapped around each common carotid artery (CCA). Within 20 min of CCA cooling, brain temperature could be lowered by 2-5 degrees C below the baseline and maintained stable for approximately 2 h while maintaining body temperature at 37 degrees C. No adverse effects of SBC were observed on systemic physiology, regional cerebral blood flow (rCBF), bleeding time, or tissue histology in normal animals. In rats having sustained 2-h MCAo, intra-ischemic SBC for 90 min, initiated 30 min following the onset of ischemia, significantly reduced infarction measured at 24 h post-injury (normothermic rats=312+/-51 mm3, SBC rats=139+/-83 mm3). In subgroup experiments, the incidence of peri-infarct depolarization (PID) was assessed during the MCAo and cooling period. Compared to normothermic but ischemic rats, SBC significantly reduced the number of PID events from 6.2+/-2.5 to 2.0+/-2.5, and reduced infarct volumes from 323+/-79 to 139+/-102 mm3. In conclusion, this extralumimal cooling method of SBC provides a safe and efficient approach to rapidly and safely achieve hypothermic neuroprotection.