Isoflurane Induces Learning Impairment That Is Mediated by Interleukin 1β in Rodents

Abstract

Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. Isoflurane can impair cognitive functions of animals under certain conditions. However, the mechanisms for this impairment are not clear. Here, male 18-month old Fisher 344 rats or 10-week old mice were exposed to 1.2 or 1.4% isoflurane for 2 h. Our studies showed that isoflurane impaired the cognitive functions of the rats in Barnes maze. Isoflurane-exposed rats had reduced freezing behavior during the training sessions in the fear conditioning test. This isoflurane effect was attenuated by lidocaine, a local anesthetic with anti-inflammatory property. Rats that had training sessions and were exposed to isoflurane 30 min later had freezing behavior similar to that of control animals. Isoflurane increased the expression of interleukin 1β (IL-1β), interleukin-6 and activated caspase 3 in the hippocampus of the 18-month old rats. IL-1β positive staining was co-localized with that of NeuN, a neuronal marker. The increase of IL-1β and activated caspase 3 but not interleukin-6 was attenuated by lidocaine. Isoflurane also impaired the cognitive functions of 10-week old C57BL/6J mice and increased IL-1β in their hippocampi. However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.

Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain

“…Neuroinf lammation contributes to volatile anesthetic-induced cognitive deficits and it has been demonstrated that isoflurane induces learning impairment by activating the NF-κB pathway and upregulating the expression of hippocampal interleukin-1β in rodents (39,40). Sevoflurane also increases levels of the pro-inflammatory cytokine interleukin-6 and tumor necrosis factor-α in the developing mouse brain (7).…”

Neuroprotective effect of paeonol against isofluraneinduced neuroapoptosis and cognitive dysfunction

“…Isoflurane has been reported to induce neuroinflammation [5]. More notably, IL-1β is associated with isoflurane-induced cognitive impairment [5].…”

“…More notably, IL-1β is associated with isoflurane-induced cognitive impairment [5]. Elevated cytosolic Ca 2+ levels induced by isoflurane has been demonstrated to activate the NF-kB signalling pathway [24] that stimulates the activation of pro-inflammatory cytokines [24].…”

“…Neuroinflammation has been reported to be involved in volatile anesthetic-induced neuroapoptosis and cognitive impairments [5]. Isoflurane induces striking increase in intracellular calcium levels [Ca 2+ ]i and this overload has been found to activate mitochondrial apoptotic pathway [6] and also the c-Jun N-terminal kinase (JNK) [2].…”

Sampling Blood from the Lateral Tail Vein of the Rat

“…First, it does not require anesthesia, in contrast with sampling from the jugular vein or retroorbital sinus. When blood samples are collected surrounding behavioral procedures, administration of anesthetics is undesirable because it can interfere with learning and memory 4,5 . Second, it offers the ability to collect larger blood volumes than other venipuncture techniques, such as collection from the saphenous or dorsal pedal veins.…”