Serial electrical stimulations of hypothalamic Orexin-containing neuronal regions lead to elevation of CSF OrexinA concentration, shorten anesthesia time and fasten recovery of normal sleep cycles from deep anesthesia induced sleep

Abstract

Introduction The aim of the study was to assess the hypothalamic Orexinergic system as the neuronal substrate for speeding up regulation of disturbed sleep homeostasis and recovery of sleep-wakefulness cycle in different behavioral states from some pathological conditions, namely from deep anesthesia induced sleep. Pre-clinical evidence in relation to this question are very sparse and therefore their investigation is highly topical. Materials and methods In white wild rats ( n = 12) after Surgical implantation of recording electrodes and postoperative recovery deep anesthesia was induced by chloralhidrate and/or sodium ethaminal. EEG registration was started immediately and lasted continuously for 48 h. 10 min after administration of anesthetic drugs serial electrical stimulations (8–12 v, 200 c/s, 0.1 ms) of dorsal, lateral, posterior and perifornical hypothalamic Orexin-containing neurons were started. Stimulations lasted for 1 h with the 5 min intervals between subsequent ones applied by turn to the left and right side hypothalamic parts. CSF OrexinA concentration was measured by ELISA method. Statistical processing was made by Students’ t -test. Results Spontaneous recovery of the first fragments of EEG wakefulness from deep anesthesia-induced sleep required 5.0–5.5 h depending on the depth of narcosis. Serial electrical stimulations of dorsal, lateral, posterior and perifornical hypothalamic Orexin-containing neurons significantly speed up wakefulness recovery from both types of narcotic sleep with the first fragments of wakefulness appearing 3.5–4 h after deep anesthesia. The first fragments of wakefulness were rapid (20–30 min) followed by normal deep slow wave sleep episodes. Especially strong influence of serial electrical stimulations of hypothalamic Orexin neuron containing parts was manifested in the recovery of REM sleep. Spontaneous recovery of this behavioral state took 23–24 h after deep anesthesia but under the impact of electrical stimulations of above mentioned hypothalamic parts REM latency became more than two times shorter. Significant elevation was noted in CSF OrexinA concentration in stimulated animals. Conclusion Serial electrical stimulations of hypothalamic Orexin-containing neuronal regions significantly elevate CSF OrexinA concentration and speed up recovery of normal sleep-wakefulness cycle behavioral states from deep anesthesia-induced sleep. Acknowledgements Acknowledgements. Supported by Shota Rustaveli National Science Foundation, Grant #11/04.