Early electrophysiological and histologic changes after global cerebral ischemia in rats.
BACKGROUND
Cerebral anoxia is fundamental to morbidity and mortality after resuscitation from cardiac arrest. With no proven effective primary therapy for post-anoxic brain injury, the goal of neurologic care are supportive, to provide prognosis and prevention of further complications. With the multifaceted approach using electroencephalography (EEG), somatosensory evoked potentials (SEP), multiunit recordings, behavioral and histologic assessment, we investigated the hyperacute recovery period after resuscitation from cardiac arrest in a rat model to define the value of EEG and SEP in assessing neurologic injury.


METHODS
Two cohorts of rats were subjected to sham and graded asphyxic-cardiac arrest. EEG was collected during baseline, at injury, and 90 minutes into recovery in the first rat cohort. EEG bursting during the first 90 minutes of recovery was visually analyzed and correlated with the neurologic recovery 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 emerged from EEG isoelectricity by burst-suppression pattern during the first 90 minutes after asphyxia. Six rats in the good outcome group (NDS >60) showed increased frequency of bursting, leading to return of EEG background activity. Six rats with a bad outcome (NDS <60) had low-intensity and persistent bursting without return of EEG background activity within 90 minutes of observation. Visual assessment showed increased EEG peak burst counts during the first 90 minutes of recovery for the rats with a good outcome compared 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 cases. The recovery profile of VPL is similar to that of cortical N2O for the animal with 3 minutes of asphyxia. However, VPL response is suppressed after 7 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 intermediate 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 evoked potential (EP). The rats were killed 4 hours after asphyxia and the hematoxylin and eosin stain performed on the brains showed evidence of neuronal injury in the thalamic reticular nucleus (TRN) which seemed to correlate with the duration of asphyxia.


CONCLUSIONS
We present a multimodality assessment of early neurologic recovery following resuscitation from cardiac arrest. The recovery of bursting and 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 recording, EEG, and neurologic behavioral recovery.
Geocadin
R G
RG
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Muthuswamy
J
J
Sherman
D L
DL
Thakor
N V
NV
Hanley
D F
DF
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000473:pathology / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009207:Myoclonus / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020651:Ventral Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology