Object
Using autoradiographic image averaging, the authors recently described prominent foci of marked glucose metabolism-greater-than-blood-flow uncoupling in the acutely traumatized rat brain. Because hypothermia is known to ameliorate injury in this and other injury models, the authors designed the present study to assess the effects of post-traumatic therapeutic hypothermia on the local cerebral metabolic rate of glucose (LCMRglu) and local cerebral blood flow (LCBF) following moderate parasagittal fluid-percussion head injury (FPI) in rats.
Methods
Either cranial hypothermia (30°C) or normothermia (37°C) was induced for 3 hours in matched groups of rats immediately after FPI; LCMRglu and LCBF were assessed 3 hours after concluding these temperature manipulations.
In rats subjected to FPI, regardless of whether normothermia or hypothermia ensued, LCBF was reduced relative to the sham-injury groups. In addition, when FPI was followed by hypothermia (FPI–30°C group), the subsequent LCBF was significantly lower (35–38% on average) than in FPI–37°C rats. Statistical mapping of LCBF difference imaging data revealed confluent cortical and subcortical zones of significantly reduced LCBF (largely ipsilateral to the prior injury) in FPI–30°C rats relative to the FPI–37°C group. Local glucose utilization was reduced in both hemispheres of FPI–37°C rats relative to the sham-injury group and was lower in the right (traumatized) hemisphere than in the left. However, LCMRglu values were largely unaffected by temperature manipulation in either the FPI or sham-injury groups. The LCMRglu/LCBF ratio was nearly doubled in FPI–30°C rats relative to the FPI–37°C group, in a diffuse and bihemispheric fashion. Linear regression analysis comparing LCMRglu and LCBF revealed that the FPI–37°C and FPI–30°C data sets were completely nonoverlapping, whereas the two sham-injury data sets were intermixed.
Conclusions
Despite its proven neuroprotective efficacy, early posttraumatic hypothermia (30°C for 3 hours) nonetheless induces a moderate decline in cerebral perfusion without the (anticipated) improvement in cerebral glucose utilization, so that a state of mild metabolism-greater-than-blood-flow dissociation is perpetuated.
Effect of TTC-909 on infarct size, ischemic brain edema, local cerebral blood flow (LCBF) and glucose utilization (LCGU) in chronic middle cerebral artery (MCA) occlusion in the stroke-prone spontaneously hypertensive rat (SHRSP)