Maternal diet pregnancy and lactation is vital to the early life neuro programming of offspring. One-carbon (1C) metabolism, which includes folic acid and choline, plays a vital role in closure of the neural tube and other neurodevelopment. However, the impact of maternal dietary deficiencies on offspring neurological function following ischemic stroke later in life remains undefined. Stroke is one of the leading causes of death globally, and its prevalence is expected to increase in younger age groups as the incidence of various risk factors for stroke increases. Furthermore, our group has shown that dietary deficiencies in 1C metabolism result in worse stroke outcome. Our study aimed to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcome in middle-aged male and female mice. Female mice were maintained on either a control or deficient diets prior to and during pregnancy and lactation. When female and male offspring were 10-months of age, ischemic stroke was induced via photothrombosis targeting the sensorimotor cortex. Stroke outcome was assessed by measuring motor function in living animals and ischemic damage volume, neurodegeneration, neuroinflammation, and choline metabolism in the brain postmortem. No significant difference was observed between maternal dietary groups in offspring motor function; however, males and females differed in their motor function. Maternal diet significantly impacted ischemic damage volume. Male and female offspring from deficient mothers showed significantly reduced neurodegeneration and neuroinflammation within the ischemic damage region. We also report changes in plasma 1C metabolites as a result of maternal diet and sex after ischemic stroke in offspring. Our data indicates that maternal dietary deficiencies do not impact offspring motor outcome following ischemic stroke, but do play a role in other ischemic stroke outcomes such as ischemic damage volume and plasma 1C metabolites in middle-aged adult offspring. Furthermore, our data indicates that sex of mice plays an important role in stroke outcome during middle-age.

Maternal dietary levels of one-carbon (1C) metabolites (folic acid and choline) during pregnancy play a vital role in neurodevelopment. However, the impact of maternal dietary deficiencies on offspring stroke outcomes later in life remains undefined. The aim of this study was to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcomes in middle-aged offspring. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. At 10 months of age ischemic stroke was induced in male and female offspring. Stroke outcome was assessed by measuring motor function and brain tissue. There was no difference in offspring motor function; however, sex differences were present. In brain tissue, maternal dietary deficiency increased ischemic damage volume and offspring from deficient mothers had reduced neurodegeneration and neuroinflammation within the ischemic region. Furthermore, there were changes in plasma 1C metabolites as a result of maternal diet and sex. Our data indicate that maternal dietary deficiencies do not impact offspring behavior after ischemic stroke but do play a role in brain histology and one-carbon metabolite levels in plasma. Additionally, this study demonstrates that the sex of mice plays an important role in stroke outcomes.

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Maternal one-carbon metabolism, including dietary levels of folic acid and choline, play an important role in early life programming. There is a well-established connection between the fetal environment and the health status of offspring. However, there is a gap in knowledge on how maternal nutrition will affect the health status of the offspring after a cardiovascular event like ischemic stroke. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3- and 10-month-old male and female offspring. Adult female mice were fed a folic acid deficient diet (FADD), a choline deficient diet (ChDD), or a control diet (CD) four weeks prior to pregnancy to deplete stores, they were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a control diet and at 2 or 10 months of age were subject to ischemic stroke within the sensorimotor cortex via the photothrombosis ischemic damage model. At 3 or 11 months of age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S -adenosylmethionine in liver tissue compared to controls. In offspring after ischemic stroke, motor function was impaired in 3-month-old male and female offspring from deficient mothers compared to control diet offspring. In 11-month-old mice there was no impact of maternal diet on motor function, but we observed sex differences. Male middle-aged adult mice had worse motor function compared to female offspring. In brain tissue, there was no impact of maternal diet on ischemic damage volume in 3-month-old animals. Interestingly, maternal diet impacted ischemic damage in 10-month-old male and female offspring. Neurodegeneration and choline metabolism in ischemic brain tissue was also impacted in 3 and 11-month-old offspring. The findings of our study suggest that a maternal diet deficient in either choline or folic acid impacts stroke outcome in young animals compared to middle-aged animals. These results points to the important role of the maternal diet in early life programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.

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