Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.

Isoflurane Anesthesia Induced Persistent, Progressive Memory Impairment, Caused a Loss of Neural Stem Cells, and Reduced Neurogenesis in Young, but Not Adult, Rodents

“…synaptogenesis, are more sensitive to isoflurane toxicity, as judged by persistent memory deficits (Jevtovic-Todorovic et al, 2003). Our data failed to find major differences in synapsin immunoreactivity, but could not rule out functional synaptic deficits.…”

“…This hypothesis was based on recent work showing that isoflurane exposure during early postnatal development resulted in increased apoptosis and subsequent behavioral impairment (Jevtovic-Todorovic et al, 2003) and a recent study showing an association between the cumulative duration of anesthesia exposure and later development of learning disabilities in children younger than 4 years of age (Wilder et al, 2009). To our surprise, repeated isoflurane exposure did induce long-lasting, even progressive, impairment of recognition and reversal learning, but had no effect on cell death of neurons or neuronal progenitors in the young, still growing brain.…”

“…Isoflurane has long been considered safe and even neuroprotective in cell culture and animal models (Popovic et al, 2000;Sakai et al, 2007). Recent findings indicate that increased activation of GABA A receptors or decreased excitation of N-methyl-D-aspartate receptors could induce widespread neurodegeneration in the developing brain (Ikonomidou et al, 1999;Jevtovic-Todorovic et al, 2003). A recent population-based cohort study showed that early exposure to anesthesia was a significant risk factor for later development of learning disabilities (Wilder et al, 2009) and concerns have been raised regarding the use of anesthetics in pediatric patients.…”

“…A recent population-based cohort study showed that early exposure to anesthesia was a significant risk factor for later development of learning disabilities (Wilder et al, 2009) and concerns have been raised regarding the use of anesthetics in pediatric patients. Neurons in the developing brain are particularly vulnerable to isoflurane (Jevtovic-Todorovic et al, 2003). Immature rats exposed to isoflurane displayed persistent memory and learning deficits, and this was associated with widespread caspase-3 activation and neuronal apoptosis (Culley et al, 2004;JevtovicTodorovic et al, 2003;Yon et al, 2005;Zhang et al, 2008).…”

The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain

“…We therefore applied in vivo 1 HMRS to investigate the effects of two different anesthetics (isoflurane and propofol) on the metabolomic profiles in the rat brain. Specifically, we chose to focus on the hippocampus and the parietal cortex given their role in memory formation and visual spatial processing, respectively, which are cognitive domains reported to be affected after general anesthesia and surgery exposures (Jevtovic-Todorovic et al, 2003;Zhu et al, 2010). Given the dissimilar uncoupling effects of the two anesthetics on CMRglu, cerebral blood flow, and electroenchephalographic (EEG) activity (Akrawi et al, 1996), we hypothesized that their corresponding metabolomic profiles would be distinct and reflect differences in spectral signatures related to Glu (excitatory neurotransmission) and possibly glucose (Glc) metabolites.…”