We appreciate the fact that Dr. Shear took an interest in our recent study showing spatial memory impairment in the adult male offspring of pregnant rats exposed to isoflurane.1His analogy that the brain is like a water trap is silly, and the argument that 4 h of anesthesia during rat gestation is equivalent to a weekend of anesthesia in humans, and therefore not clinically relevant, is mathematically correct but scientifically simplistic. The rat brain and human brain are obviously different. In comparison with that of the rat, for example, the human brain has approximately 430-fold more neurons, a more intricate dendritic arbor, and a markedly larger and more complicated cortical surface (accounting for 77% of brain volume vs.  just 30% in the rat).2,3Of particular relevance for gestational exposure to anesthetics, the human brain has more neural stem cells, which have threefold more mitotic cycles and must traverse far longer distances to reach the right place at the right time than those in the rat. In addition, there is the fact that the human brain does far more complicated things (such as math), which requires more precise and complex connections and circuits. In short, the human brain is exponentially more intricate than the rodent brain. This is why we were careful not to extrapolate our results in the rodent to humans. More to the point, however, to the extent vulnerability is proportional to complexity (see recent events on Wall Street), it is quite plausible that the developing human brain is actually more easily damaged by general anesthetics than the rodent brain or, alternatively, that the consequences of injury are more noticeable because the demands on the system are greater in humans. Humans, for instance, are more sensitive to perinatal asphyxia-induced neuronal injury than rats.4Moreover, we know from recent studies in neonatal monkeys, a species phylogenetically closer to humans than rats, that it does not take a weekend of anesthesia to induce a 13-fold increase in neuronal degeneration—5 h of isoflurane will do it.5The answer to whether general anesthetics harm the developing human central nervous system will come only from research, not simple math that fails to take into account the myriad differences between the rodent and human brain. In the meantime, we recommend focusing scientific debate on how general anesthetics may affect “plasticity” of the human brain rather than the plastic in water traps.

Palanisamy A, Baxter MG, Keel PK, Xie Z, Crosby G, Culley DJ: Rats exposed to isoflurane in utero  during early gestation are behaviorally abnormal as adults. ANESTHESIOLOGY 2011; 114:521–8
Ang ES Jr, Gluncic V, Duque A, Schafer ME, Rakic P: Prenatal exposure to ultrasound waves impacts neuronal migration in mice. Proc Natl Acad Sci USA 2006; 103:12903–10
Herculano-Houzel S: The human brain in numbers: A linearly scaled-up primate brain. Front Hum Neurosci 2009; 3:31
Vannucci RC, Vannucci SJ: Perinatal hypoxic-ischemic brain damage: Evolution of an animal model. Dev Neurosci 2005; 27:81–6
Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, Dissen GA, Creeley CE, Olney JW: Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. ANESTHESIOLOGY 2010; 112:834–41