Physiological Disturbance May Contribute to Neurodegeneration Induced by Isoflurane or Sevoflurane in 14 Day Old Rats

Abstract

BackgroundVolatile anesthetics are widely used in pediatric anesthesia but their potential neurotoxicity raise significant concerns regarding sequelae after anesthesia. However, whether physiological disturbance during anesthetic exposure contributes to such side effects remains unknown. The aim of the current study is to compare the neurotoxic effects of isoflurane and sevoflurane in 14 day old rat pups under spontaneous breathing or ventilated conditions.MethodsPostnatal 14 day rats were assigned to one of five groups: 1) spontaneous breathing (SB) + room air (control, n = 17); 2) SB + isoflurane (n = 35); 3) SB + sevoflurane (n = 37); 4) mechanical ventilation (MV) + isoflurane (n = 29); 5) MV + sevoflurane (n = 32). Anesthetized animal received either 1.7% isoflurane or 2.4% seveoflurane for 4 hours. Arterial blood gases and blood pressure were monitored in the anesthetized groups. Neurodegeneration in the CA3 region of hippocampus was assessed with terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling immediately after exposure. Spatial learning and memory were evaluated with the Morris water maze in other cohorts 14 days after experiments.ResultsMost rats in the SB groups developed physiological disturbance whereas ventilated rats did not but become hyperglycemic. Mortality from anesthesia in the SB groups was significantly higher than that in the MV groups. Cell death in the SB but not MV groups was significantly higher than controls. SB + anesthesia groups performed worse on the Morris water maze behavioral test, but no deficits were found in the MV group compared with the controls.ConclusionsThese findings could suggest that physiological disturbance induced by isoflurane or sevoflurane anesthesia may also contribute to their neurotoxicity.

Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen–Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma

“…However, consistent with previous studies, exposure to 2 % sevoflurane post-conditioning could significantly increase neuronal cell viability and reduced neuronal cell death compared with 1 or 4 % [1]. In addition, with extending the post-conditioning exposure time, the toxicity of sevoflurane to neuron was gradually presented, so post-conditioning for 1 h after OGD was carried out to apply [26,27]. Moreover, from the result of neuron/astrocyte ratio, no significant changes were found between control and different concentrations of sevoflurane.…”

A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research

“…In this regard, Wu et al . showed that the neuronal damage caused by isoflurane or sevoflurane was attenuated if the animal was mechanically ventilated rather than being allowed to breath spontaneously. Furthermore, gender appears to be an independent risk factor, and male and female animals exposed to equivalent doses of anesthetics can have different long‐term cognitive impairment.…”

Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery: A randomized controlled study comprising four different anaesthetic techniques

“…Wu et al (2014) compared the effect of mechanical ventilation and spontaneous breathing in young rats receiving isoflurane or sevoflurane. Mechanical ventilation induced higher pO 2 and lower pCO 2 .…”

“…The rats were breathing spontaneously with relative high concentrations of oxygen leading to hyperoxia, which may influence neuroapoptosis as well as induce retinopathy (Ahdab-Barmada et al, 1986;Penn et al, 1994;Porzionato et al, 2013). Wu et al (2014) compared the effect of mechanical ventilation and spontaneous breathing in young rats receiving isoflurane or sevoflurane. Mechanical ventilation induced higher pO 2 and lower pCO 2 .…”