Posttraumatic hypothermia followed by slow rewarming protects the cerebral microcirculation

In the clinical and laboratory setting, multiple reports have suggested the efficacy of hypothermia in blunting the damaging consequences of traumatic brain injury (TBI). With the use of posttraumatic hypothermia, it has been recognized that the time of initiation and duration of hypothermia are important variables in determining the degree of neuroprotection provided. Further, it has been recently recognized that the rate of posttraumatic rewarming is an important variable, with rapid rewarming exacerbating neuronal/axonal damage in contrast to slow rewarming which appears to provide enhanced neuroprotection. Although these findings have been confirmed in the brain parenchyma, no information exists for the cerebral microcirculation on the potential benefits of posttraumatic hypothermia followed by either slow or rapid rewarming. In the current communication we assess these issues in the pial circulation using a well-characterized model of TBI. Rats were prepared for the placement of cranial widows for direct assessment of the pial microcirculation prior to and after the induction of impact acceleration injury followed by moderate hypothermia with either subsequent slow or rapid rewarming strategies. The cranial windows allowed for the measurement of pial vessel diameter to assess ACh-dependent and CO2 reactivity in the chosen paradigms. ACh was applied topically to assess ACh-dependent dilation, while CO2 reactivity was assessed by changing the concentration of the inspired gas. Through this approach, it was found that posttraumatic hypothermia followed by slow rewarming maintained normal arteriolar vascular responses in terms of ACh-dependent dilation and CO2 reactivity. In contrast, arterioles subjected to TBI followed by normothermia or hypothermia and rapid rewarming showed impaired vasoreactivity in terms of their ACh-dependent and CO2 responses. This study provides additional evidence of the benefits of posttraumatic hypothermia followed by slow rewarming, demonstrating for the first time that the previously described neuroprotective effects extend to the cerebral microcirculation.