TY - JOUR
T1 - The ventrolateral preoptic nucleus is not required for isoflurane general anesthesia
AU - Eikermann, Matthias
AU - Vetrivelan, Ramalingam
AU - Grosse-Sundrup, Martina
AU - Henry, Mark E.
AU - Hoffmann, Ulrike
AU - Yokota, Shigefumi
AU - Saper, Clifford B.
AU - Chamberlin, Nancy L.
N1 - Funding Information:
This work was supported by grants from the National Institute of Health (Bethesda, MD, USA, P50 HL060292, HL095491, AG09975 and NS072337 ), and a grant from the German Research Council ( DFG-EI684/2-1 ).
PY - 2011/12/2
Y1 - 2011/12/2
N2 - Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. We tested whether destruction of the VLPO neurons would affect the onset, depth, or recovery from isoflurane's general anesthetic effects. The VLPO was ablated in 25 rats by bilateral local injection of orexin-saporin, and polysomnography was performed to measure baseline sleep loss and responses to isoflurane anesthesia at 1% and 2%. Eight rats received sham (saline) injections. We measured isoflurane effects on time to loss of righting reflex, onset of continuous slow wave activity, and burst suppression; burst-suppression ratio; and time to recovery of righting reflex and desynchronized EEG. VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r = 0.77 and r = 0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (- 0.59), increased burst-suppression ratio (r = 0.52), and increased emergence time (r = 0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p < 0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for isoflurane anesthesia.
AB - Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. We tested whether destruction of the VLPO neurons would affect the onset, depth, or recovery from isoflurane's general anesthetic effects. The VLPO was ablated in 25 rats by bilateral local injection of orexin-saporin, and polysomnography was performed to measure baseline sleep loss and responses to isoflurane anesthesia at 1% and 2%. Eight rats received sham (saline) injections. We measured isoflurane effects on time to loss of righting reflex, onset of continuous slow wave activity, and burst suppression; burst-suppression ratio; and time to recovery of righting reflex and desynchronized EEG. VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r = 0.77 and r = 0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (- 0.59), increased burst-suppression ratio (r = 0.52), and increased emergence time (r = 0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p < 0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for isoflurane anesthesia.
KW - Hypothalamus
KW - Isoflurane
KW - Rat
KW - Sleep
KW - Sleep deprivation
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U2 - 10.1016/j.brainres.2011.10.018
DO - 10.1016/j.brainres.2011.10.018
M3 - Article
C2 - 22041226
AN - SCOPUS:81155131308
SN - 0006-8993
VL - 1426
SP - 30
EP - 37
JO - Brain Research
JF - Brain Research
ER -