The Effect of Sevoflurane on Neuronal Degeneration and GABAA Subunit Composition in a Developing Rat Model of Organotypic Hippocampal Slice Cultures

Abstract

This in vitro investigation supports an age-dependent and GABA(A) receptor subunit composition relationship between 2.0% sevoflurane exposure and cell death.

In Vivo Monitoring of Sevoflurane-induced Adverse Effects in Neonatal Nonhuman Primates Using Small-animal Positron Emission Tomography

“…[17][18][19][20] in a neonatal rat model, a single episode of sevoflurane-induced general anesthesia (2 to 2.5% for 4 to 6 h) leads to widespread neuronal apoptosis in several brain regions and causes long-term behavioral impairments and memory dysfunction. 4,15,[21][22][23] Repeated treatments with sevoflurane during gestation in the rat induced neuronal apoptosis in the brains of offspring. 24 in the mouse, exposure to sevoflurane on postnatal day (Pnd) 7 induced neuroapoptosis in the hippocampal region.…”

Anesthesia and the Developing Brain: Relevance to the Pediatric Cardiac Surgery

“…, midazolam, nitrous oxide and isoflurane, promoted neuronal cell death and long-term memory deficits in a neonatal rat pup model of developing brain [5]. What followed from this was a flurry of in vitro and in vivo studies further confirming that isoflurane, when given for 5–6 h, at a critical period in development, 4–6 days in a rodent, caused anesthetic neurotoxicity [7,18,22]. These manuscripts were criticized mainly for their inability to mimic the “true “conditions of an anesthetic in an infant or young child.…”

“…Several animal investigations ( in vitro and in vivo ) followed to assess independently the effect of pH and carbon dioxide control, and surgical stimulation and its effect on anesthetic neurotoxicity [18,22,60,61,62,63,64]. These studies found that in the presence of pH control, isoflurane had an age-and duration-dependent effect on anesthetic neurotoxicity [18,22]. Hypercarbia, alone, promoted neurodegeneration similar to that observed with anesthesia alone in PND7 rat pups [62,63].…”

“…Investigations with isoflurane have included rodents and more recently non-human primates [71,72,73]. Evidence is conclusive in developing models of in vitro and in vivo rodent brain that isoflurane provides a duration- and dose-dependent effect on neuronal cell death [5,18,22]. Studies have looked at sevoflurane, independently and in comparison to isoflurane, and have found neuronal cell death as well [6,8,19,20,21,66,68,70].…”

“…These neurologic outcome studies are specific to the preterm [9,10,11] and congenital heart disease populations [12,13,14,15,16,17]. With the recent concern of anesthetic neurotoxicity in the developing brain, mostly from laboratory investigations [5,6,7,8,18,19,20,21,22] the neurologic assessment of children after anesthetic exposure at a young age is now being emphasized [23,24,25,26,27,28,29,30]. …”