Retardation of brain growth of guinea pigs by hyperthermia: Effect of varying intervals between successive exposures

Abstract

Guinea pigs were exposed to a temperature of 42.5–43.5°C on three occasions between days 20 and 23 of pregnancy. In the first experiment, groups of mothers were exposed at intervals of 18–30 hr. Each exposure ended when the deep rectal temperature had been over 43°C for 6 min and mean temperatures were 43.2–43.4°C. Micrencephaly was found in 78% of heated newborn offspring, the mean brain weights of all groups being significantly less than controls. In the heated groups, the brain weights were reduced significantly as the interval between exposures decreased. Abnormalities other than micrencephaly were found in 10% of heated offspring and included exomphalos, clubfoot, and hypodactyly. In the second experiment, groups of mothers were exposed for 1 hour at intervals of 6–20 hr. The mean temperatures of heated groups were 42.6–42.9°C. The mean brain weights of all groups of heated newborn were significantly reduced and micrencephaly was found in 61% of newborn. Brain weights were reduced significantly as mean maternal temperature increased. There was a significant interaction between the level of temperature elevation and the interval between exposures. Intervals of 6, 8, and 12 hr induced large deficits in brain growth even when temperature elevations were small. We hypothesize that the initial exposure might partially synchronize the brain cell generation cycle, causing abnormally large numbers of cells to be in mitosis 6–8 hr later and thus at risk to lethal damage by a second or third hyperthemic exposure.