title: Intraventricular orexin-A improves arousal and early EEG entropy in rats after cardiac arrest.
abstract: The recovery of arousal after cardiac arrest (CA) is associated with evolution from electroencephalographic (EEG) burst-suppression to continuous activity. Orexin-A elicits arousal EEG during anesthetic burst-suppression. We hypothesized that orexin-A would improve arousal and EEG entropy after CA. Eighteen Wistar rats were subjected to 7-minute asphyxial CA and resuscitation. Rats were divided into treatment (n=9) and control (n=9) groups. Twenty minutes after resuscitation, the treatment group received 0.1 mL of 1 nM orexin-A intraventricularly, while controls received saline. EEG was quantified using Information Quantity (IQ), a measure of entropy validated for detection of burst-suppression and arousal patterns. IQ values range from 0 to 1.0. Arousal was quantified using the neurological deficit scale (NDS). The ischemic neuronal fraction of hippocampus CA1 and cortex was histologically determined. Baseline and post-resuscitation characteristics were similar between the groups. The NDS score (mean+/-SD) at 4 h was higher in the orexin-A group compared to controls (57.3+/-5.8 vs. 40.7+/-5.9, p<0.02), but scores were similar at 72 h. Burst frequency was similar in both groups but the orexin-A group demonstrated higher IQ values compared to controls beginning within 10 min. IQ values remained significantly higher in the orexin-A group for the first 120 min (p=0.008) and subsequently converged. The ischemic neuronal fraction was similar between groups in cortex (p=0.54) and hippocampus CA1 (p=0.14). In rats resuscitated from CA, orexin-A transiently increased arousal and EEG entropy without worsening ischemic neuronal injury. The role of orexin-A in recovery of arousal after CA deserves further investigation.
authors.affiliation: The Johns Hopkins University School of Medicine, 600 N. Wolfe St, Meyer 8-140, Baltimore, MD 21287, USA. mkoenin1@jhmi.edu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Koenig
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Jia
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Kang
authors.forename: Adrian
authors.initials: A
authors.lastname: Velasquez
authors.forename: Nitish V
authors.initials: NV
authors.lastname: Thakor
authors.forename: Romergryko G
authors.initials: RG
authors.lastname: Geocadin
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology*; D001237:Asphyxia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D019277:Entropy; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009479:Neuropeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins