Early electrophysiological and histologic changes after global cerebral ischemia in rats

INTRODUCTION: Cerebral anoxia is fundamental to morbidity and mortality aft er resuscitation from cardiac arrest. With no proven effective primary ther apy for post-anoxic brain injury, the goal of neurologic care are supportiv e, to provide prognosis and prevention of further complications. With the m ultifaceted approach using electroencephalography (EEG), somatosensory evok ed potentials (SEP), multiunit recordings, behavioral and histologic assess ment, we investigated the hyperacute recovery period after resuscitation fr om cardiac arrest in a rat model to define the value of EEG and SEP in asse ssing neurologic injury. METHODS: Two cohorts of rats were subjected to sham and graded asphyxic-car diac arrest. EEG was collected during baseline, at injury, and 90 minutes i nto recovery in the first rat cohort. EEG bursting during the first 90 minu tes of recovery was visually analyzed and correlated with the neurologic re covery at 24 hours after injury. The neurologic recovery was assessed using a neurodeficit score (NDS) with 80 as normal and 0 as brain dead. The next rat cohort subjected to asphyxic-cardiac arrest was studied using SEP and multiunit recording in the VPL; brain histologic studies were performed at 4 hours after the asphyxia. RESULTS: The first rat cohort subjected to graded asphyxic-cardiac arrest e merged from EEG isoelectricity by burst-suppression pattern during the firs t 90 minutes after asphyxia. Six rats in the good outcome group (NDS >60) s howed increased frequency of bursting, leading to return of EEG background activity. Six rats with a bad outcome (NDS <60) had law-intensity and persi stent bursting without return of EEG background activity within 90 minutes of observation. Visual assessment showed increased EEG peak burst counts du ring the first 90 minutes of recovery for the rats with a good outcome comp ared with the rats with a bad outcome. In the second cohort, the rats were subjected to 3 minutes, 5 minutes, and 7 minutes of asphyxia. The N20 recovered to 60% of baseline in all three ca ses. The recovery profile of VPL is similar to that of cortical N20 for the animal with 3 minutes of asphyxia. However, VPL response is suppressed aft er T minutes of asphyxia leading to a divergence in the rate of recovery of the cortical N20 and VPL response. In both the animals (with mild and inte rmediate injury) in which the early response in VPL recovered to more than 50% of baseline, the recovery profile was similar to the N20 in cortical ev oked potential (EP). The rats were killed 4 hours after asphyxia and the he matoxylin and eosin stain performed on the brains showed evidence of neuron al injury in the thalamic reticular nucleus (TRN) which seemed to correlate with the duration of asphyxia. CONCLUSION: We present a multimodality assessment of early neurologic recov ery following resuscitation from cardiac arrest. The recovery of bursting a nd high-frequency oscillations may be regulated by interneurons in the TRN. The early selective vulnerability of these interneurons in the TRN may be crucial to the early neurologic recovery as assessed by EP, multiunit recor ding, EEG, and neurologic behavioral recovery.