The fetus is strongly dependent on nutrients from the mother, including
polyunsaturated fatty acids (PUFA). In adult animals,
n-3 PUFA ameliorates
stroke-mediated
brain injury, but the modulatory effects of different PUFA content in maternal diet on focal arterial
stroke in neonates are unknown. This study explored effects of maternal n-3 or n-6 enriched PUFA diets on neonatal
stroke outcomes. Pregnant mice were assigned three isocaloric diets until offspring reached postnatal day (P) 10-13: standard, long-chain
n-3 PUFA (n-3) or n-6 PUFA (n-6) enriched.
Fatty acid profiles in plasma and brain of mothers and pups were determined by gas chromatography-mass spectrometry and
cytokines/
chemokines by multiplex
protein analysis. Transient
middle cerebral artery occlusion (tMCAO) was induced in P9-10 pups and
cytokine and
chemokine accumulation,
caspase-3 and
calpain-dependent
spectrin cleavage and
brain infarct volume were analyzed. The n-3 diet uniquely altered brain
lipid profile in naïve pups. In contrast,
cytokine and
chemokine levels did not differ between n-3 and n-6 diet in naïve pups. tMCAO triggered accumulation of inflammatory
cytokines and caspase-3-dependent and -independent cell death in ischemic-reperfused regions in pups regardless of diet, but magnitude of
neuroinflammation and
caspase-3 activation were attenuated in pups on n-3 diet, leading to protection against neonatal
stroke. In conclusion, maternal/postnatal n-3 enriched diet markedly rearranges neonatal brain
lipid composition and modulates the response to
ischemia. While standard diet is sufficient to maintain low levels of inflammatory
cytokines and
chemokines under physiological conditions,
n-3 PUFA enriched diet, but not standard diet, attenuates increases of inflammatory
cytokines and
chemokines in ischemic-reperfused regions and protects from neonatal
stroke.