Pharyngeal Selective Brain Cooling Improves Neurofunctional and Neurocognitive Outcome after Fluid Percussion Brain Injury in Rats

Abstract

Therapeutic hypothermia (TH) after cardiac arrest reduces mortality and improves neurological outcome. Experimental TH after traumatic brain injury (TBI) indicated similar effects, but benefits were not reproducible in large clinical trials. Therefore, a novel approach of pharyngeal selective brain cooling (pSBC) was tested in respect to neurological outcome in a model of experimental TBI. Male Sprague-Dawley rats were subjected to lateral fluid percussion (LFP) brain injury and received pSBC for 3h post-injury. All animals were examined for neuromotor and sensorimotor dysfunction and coordination: before and after injury, and during recovery on day post-injury (DPI) 7 and 14 using (i) the standardized Composite Neuroscore (NS) test and (ii) the Rotarod test. Recovery of cognitive function was assessed on days 10-14 using (iii) the Barnes Circular Maze (BCM). In pSBC-animals, brain temperature was selectively lowered to 33 +/- 0.5 degrees C at 15 min post-injury, keeping rectal temperature at a physiologic level. All animals subjected to TBI via LFP showed an identical pattern of severe neurofunctional impairment at 24 h after injury. In the time course of the experiment, pSBC-animals showed superior neurofunctional recovery on DPI 7 (p = 0.03) and 14 (p = 0.002). Similarly, distance, time, and maximum speed on the Rota-Rod were significantly increased in pSBC-animals on DPI 7 (p < 0.01) and 14 (p < 0.01), as well as latency, distance, and mean number of errors in the BCM on DPI 14 (p < 0.01). The novel approach of pSBC was associated with improved neuromotor, sensormotor, and neurocognitive outcome after experimental TBI.