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 1nM 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 0–1.0. 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 hours 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 hours. Burst frequency was similar in both groups but the orexin-A group demonstrated higher IQ values compared to controls beginning within 10 minutes. IQ values remained significantly higher in the orexin-A group for the first 120 minutes (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.

The detection of epileptic seizure signals based on fuzzy entropy

“…Furthermore, the concept of entropy has been expanded in several different fields, and some new concepts have emerged, such as sample entropy (SampEn), approximate entropy (ApEn), wavelet entropy (WE), multiscale entropy (MSE), and permutation entropy (PE). All of these indexes have been applied to varying degrees in the analyses of cognitive mental states and sleep states employing EEG signals (Koenig et al, 2009;Korotchikova et al, 2009;Takahashi et al, 2010;Yun et al, 2012). These studies demonstrate that an entropy analysis of the brain may be a promising prospect in the field of EEG-based evaluation.…”

Intranasal post-cardiac arrest treatment with orexin-A facilitates arousal from coma and ameliorates neuroinflammation

“…It originates in the hypothalamus and delivers orexin to different brain regions. Orexin-A (ORXA) is a neuropeptide that is responsible for maintaining wakefulness and is closely associated with other neurotransmitter pathways [ 9 , 12 , 13 ].…”

“…Our previous work explored ORXA as a drug that may promote arousal in an experimental setting of CA-induced coma [ 12 ]. A single intracerebroventricular (icv) injection of ORXA resulted in an improvement in the EEG-based measure of arousal at 4 hrs post CA.…”

Recovery from Coma Post-Cardiac Arrest Is Dependent on the Orexin Pathway

“…In this regard, a previous study reported that a single injection of OXA into the ventricular space immediately after resuscitation from CA led to accelerated neurological recovery of rodents. 18 It remains to be determined whether delayed, instead of early, blockade of orexin would also impair recovery. Defining this time window would help to elucidate the relationships between orexin, arousal, and the final level of neurological recovery.…”

“…18 The NDS consists of components that measure arousal, brainstem function, motor, and sensory activities. The NDS was determined at 4, 24, and 72 h post-ROSC by at least two welltrained personnel who were blind to treatments.…”