Consumption of broccoli sprouts during late gestation and lactation confers protection against developmental delay induced by maternal inflammation.

BACKGROUND: The presence of a fetal inflammatory response is linked to cerebral palsy. Unfortunately no preventive therapies are available. In this study, we determined whether dietary supplementation with broccoli sprouts (BrSp), a phase-II enzyme inducer, would be effective in preventing the behavioural and pathologic manifestations in a rodent model of inflammation during late pregnancy. METHODS: Pregnant Long-Evans rats were administered i.p. Injections of saline (100µl) or lipopolysaccharide (LPS, 200µg/kg), every 12h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3-21 followed by neuropathological analyses. RESULTS: Pups born from the LPS group were significantly growth restricted (p<0.001) and delayed in hindlimb placing (p<0.05), cliff avoidance (p<0.05), and gait (p<0.001) compared to controls. In the open field behaviour analyses, LPS pups had an increase in grooming behaviour (p<0.05) and a decreased amount of time spent in the center of the box compared to controls. Dietary supplementation with BrSp to offspring exposed to LPS had increased birth weights (p<0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p<0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls. CONCLUSIONS: Our data suggest that BrSp dietary supplementation during pregnancy may be effective in preventing growth restriction and neurodevelopmental delays.

Preventing hyperthermia decreases brain damage following neonatal hypoxic-ischemic seizures.

Neonatal seizures are the most common manifestation of underlying cerebral dysfunction. Hypoxic-ischemic encephalopathy is the cause of seizures in 40-60% of newborns. Previous work from our laboratory demonstrates that seizures associated with a hypoxic-ischemic insult results in aggravation of neuronal cell death, specifically within the hippocampus. The latter occurs in the setting of spontaneously occurring hyperthermia of 1.5 degrees C. The purpose of this study was to determine whether preventing the onset of seizure induced hyperthermia would be neuroprotective. Three groups of 10-day old rat pups received unilateral hypoxic-ischemic insults for 30 min followed by KA-induced seizures. Hyperthermia was prevented by lowering the environmental temperature ("relative hypothermia") to 29 degrees C such that the seizuring rat pups were normothermic. In one group, the prevention of hyperthermia occurred immediately following hypoxia-ischemia, whereas in the other group it occurred at the onset of seizures. The third group of rat pups (controls) remained at their nesting temperature and therefore became hyperthermic during seizures. Early (3 days) and late (20 days) neuropathology was assessed. Rat pups in whom hyperthermia was prevented during seizures displayed a significant reduction in brain damage compared to controls (p<0.05). Assessment of hippocampal brain damage also showed a significant improvement in neuronal necrosis at 20 days of recovery compared to 3 days of recovery (p<0.05). The results indicate that preventing spontaneous hyperthermia in this model of hypoxic-ischemic seizures in the newborn is neuroprotective.