Abstract
Background Nutrition is a modifiable risk factor for ischemic stroke. As people age their ability to absorb some nutrients decreases, an example is vitamin B12. Older individuals with a vitamin B12 deficiency are at a higher risk for stroke and have worse outcome. However, the mechanisms through which these occur remain unknown.
Objective The aim of the study was to investigate the role of vitamin B12 deficiency in ischemic stroke outcome in a mouse model.
Methods At 10-weeks of age male and female C57Bl/6J mice were put on vitamin B12 deficient (0 mg/kg) or control (0.025 mg/kg vitamin B12) diets for 4-weeks (n = 10/group). Using the photothrombosis model the sensorimotor cortex was damaged and at 18 weeks of age, motor outcome was measured. At the end of experiments, brain, blood, and liver tissue were collected to measure homocysteine levels, ischemic damage volume, apoptosis, or one-carbon metabolite levels.
Results All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. In ischemic brain tissue no difference between groups in lesion volume were detected. There were changes in levels of one-carbon metabolites in ischemic and non-ischemic brain tissue because of a vitamin B12 deficiency or sex. There was an increase in total apoptosis in ischemic brain tissue of male vitamin B12 deficient animals. There was more neuronal survival within ischemic brain tissue of the vitamin B12 deficient animals compared to controls. After ischemic stroke, vitamin B12 deficient male and female mice had impaired motor function compared to control animals.
Conclusions The data presented in this study confirm that a dietary vitamin B12 deficiency impacts motor function in older adult male mice after ischemic stroke. The mechanisms driving this change may be a result of neuronal survival and compensation in one-carbon metabolism within the damaged brain tissue.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Sources of support: Midwestern University Start-up Funds
Conflict of Interest and Funding Disclosure: None
Abbreviations
- tHcy
- Total homocysteine
- NeuN
- neuronal nuclei
- DAPI
- 4′,6-diamidino-2-phenylindole