A dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke to the sensorimotor cortex in middle aged male and female mice

The majority of the population is growing older, in 2000, 10% of the total population of the world was over 60 years old and the proportion is projected to increase to 21% by 2050. Currently, ischemic stroke predominately affects the elderly. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, most older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin that take place during the aging process. Using a mouse model system, we investigated the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in ischemic versus non-ischemic brain tissue. At 10-weeks of age male and female C57Bl/6J mice were put on control or vitamin B12 deficient diets for 4-weeks prior to ischemic damage. At 14 weeks of age, we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model. Animals were continued on diets for 4 weeks after damage. At 18 weeks of age, we assessed stroke outcome using the accelerating rotarod and forepaw placement tasks. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissues to assess histological and biochemical measurements. All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to control diet animals after ischemic stroke. In ischemic brain tissue no difference between groups in lesion volume was observed. More neuronal survival was present in ischemic brain tissue of the vitamin B12 deficient group compared to controls. There were changes in choline metabolites in ischemic brain tissue as a result of diet and sex. In conclusion, the data presented in this study confirms that a vitamin B12 deficiency impacts motor function in older adult male and female mice after ischemic stroke. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.

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A Dietary Vitamin B12 Deficiency Impairs Balance and Coordination After Ischemic Injury to the Sensorimotor Cortex in Adult Male and Female Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab049_045 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 932-932

Author(s):

Gyllian Yahn ◽

Brandi Wasek ◽

Terry Bottiglieri ◽

Nafisa Jadavji

Keyword(s):

Risk Factor ◽

Ischemic Stroke ◽

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

Stroke Outcome ◽

Deficient Diet ◽

Male And Female ◽

Female Mice ◽

B12 Deficiency ◽

Total Homocysteine

Abstract Objectives The majority of the world's population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Methods At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain, blood, and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue. Funding Sources Midwestern University Start-Up Funds.

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Abstract P807: Vitamin B12 Deficiency Impairs Balance and Coordination After Photothrombotic Damage to the Sensorimotor Cortex in Adult Male and Female Mice After Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p807 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Gyllian Yahn ◽

Teodoro Bottiglieri ◽

Brandi Wasek ◽

Nafisa Jadavji

Keyword(s):

Ischemic Stroke ◽

Vitamin B12 ◽

Control Diet ◽

Vitamin B12 Deficiency ◽

Stroke Outcome ◽

Deficient Diet ◽

Male And Female ◽

Female Mice ◽

B12 Deficiency ◽

Total Homocysteine

Introduction: The majority of the world’s population is growing older, in 2000, 10% of the total population of the world was over 60 years old and is projected to increase to 21% by 2050. Brain vasculature is unique, and its aging has been scarcely investigated at the cellular, and molecular levels, as well as in the context of age-related comorbidities. Nutrition is a modifiable risk factor for stroke, as people age their ability to absorb some nutrients decreases. A primary example is vitamin B12, the majority of older adults are deficient in vitamin B12 because of changes in breakdown and absorption of the vitamin. Furthermore, a vitamin B12 deficiency results in elevated levels of homocysteine which is a risk factor for cardiovascular diseases, such as stroke. Using a mouse model system, the aim of this study was to understand the role of vitamin B12 deficiency in ischemic stroke outcome and investigate mechanistic changes in the brain. Hypothesis: Vitamin B12 deficient mice will exhibit worse stroke outcome compared to control diet mice through increased apoptosis. Methods: At 10-weeks of age male and female C57Bl/6J mice were put on control (0.025 mg/kg of vitamin B12) or vitamin B12 deficient (0 mg/kg of vitamin B12) diets for 4-weeks prior to ischemic damage. At 14 weeks of age we induced ischemic stroke in the sensorimotor cortex using the photothrombosis model, all animals received damage. Animals continued on diets for 4 weeks after damage. At 18 weeks of age we assessed stroke outcome using the accelerating rotarod and forepaw placement task. After the collection of behavioral data, we euthanized animals and collected brain and liver tissue to assess histological and biochemical measurements. Plasma was used to measure total homocysteine and methylmalonic acid. Results: All animals maintained on the vitamin B12 deficient diet had increased levels of total homocysteine in plasma and liver tissue. Male and female mice maintained on a vitamin B12 deficient diet had impairments in balance and coordination on the accelerating rotarod compared to animals maintained on a control diet. Conclusions: Vitamin B12 deficiency impacts motor function in older adult male and female mice. We are investigating damage volume and potential mechanisms within the damage brain tissue.

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Hyperhomocysteinemia and Vitamin B12 deficiency as a risk factor for ischemic stroke: A case–control study from Northwestern India

Indian Journal of Health Sciences and Biomedical Research (KLEU) ◽

10.4103/kleuhsj.kleuhsj_9_18 ◽

2018 ◽

Vol 11 (3) ◽

pp. 228

Author(s):

MaulikA Panchal ◽

BanshiLal Kumawat ◽

ChandraMohan Sharma ◽

MohitJ Shah

Keyword(s):

Risk Factor ◽

Ischemic Stroke ◽

Vitamin B12 ◽

Case Control Study ◽

Vitamin B12 Deficiency ◽

Case Control ◽

Northwestern India ◽

B12 Deficiency ◽

Control Study

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Effects of near-far acupuncture on neuronal function and expression of apoptosis-related protein Bax/Bcl-2/Cleaved caspase-3 in rats with ischemic stroke

Acupuncture & Electro-Therapeutics Research ◽

10.3727/036012921x16112663844879 ◽

2021 ◽

Vol 45 (2) ◽

pp. 73-86

Author(s):

Wang Jian ◽

Zhang Can ◽

Yang Jun ◽

Xing Liwei ◽

Zhang Kun ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Infarction ◽

Brain Tissue ◽

Caspase 3 ◽

Neurological Function ◽

Acupuncture Group ◽

Sham Operation ◽

Model Group ◽

Ischemic Brain ◽

Ischemic Brain Tissue

Objectives To explore the effects of electroacupuncture on nerve function in rats with ischemic stroke and its mechanism of anti-apoptosis. Methods A total of 80 SPF male SD rats were randomly divided into sham operation group, model group, sham electroacupuncture group, acupuncture group, electroacupuncture group and 16 rats in each group. The rat model of left ischemic stroke was prepared by suture embolization. In the sham group, the left common carotid artery was isolated only and no other treatment was given. In the electroacupuncture group, "Baihui" and "Mingmen" were selected for acupuncture, followed by dilatation wave, frequency 2Hz/100Hz, intensity 1mA, and electroacupuncture for 30min. The sham electroacupuncture group was the same as the electroacupuncture group in acupoint electroacupuncture group was the same as the electroacupuncture group in acupoint selection. The electroacupuncture group was only inserted subcutaneously and then connected with the electroacupuncture group without power supply, and fixed for 30 minutes. The electroacupuncture group and the acupuncture group received electroacupuncture treatment once, for a total of 14 days, 1d after modeling. The Improved Neurological Impairment scale (mNSS) was used to evaluate the degree of neurological impairment in each group after anesthesia and wakefulness. The percentage of cerebral infarction area was determined by TTC staining. HE staining and Nissl staining were used to observe the pathological changes of ischemic brain tissue. The level of apoptosis in ischemic brain tissue was detected by TUNEL assay. Western blot was used to detect protein expression of Bax, Bcl-2 and Cleaved caspase-3 in ischemic brain tissue. Results Compared with the sham operation group, neurological function score, percentage of cerebral infarction area and apoptosis level in the model group were significantly increased (all P < 0.01). Compared with the model group, neurological function score, percentage of cerebral infarction area and apoptosis index of acupuncture group and electroacupuncture group were decreased (all P <0.05). Compared with the model group, the expression levels of Bcl-2 protein in ischemic brain tissue of rats with ischemic stroke were up-regulated in the acupuncture group and electroacupuncture group to different degrees, while the expression levels of Bax and Cleaved caspase-3 protein were down-regulated in the electroacupuncture group. Conclusion Electroacupuncture may inhibit Bax, Cleaved caspase-3 and up-regulate the expression of Bcl-2 against neuronal apoptosis, thereby improving the neurological function injury of ischemic stroke rats.

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Role of vitamin B12 deficiency in ischemic stroke risk and outcome

Neural Regeneration Research ◽

10.4103/1673-5374.291381 ◽

2021 ◽

Vol 16 (3) ◽

pp. 470

Author(s):

NafisaM Jadavji ◽

GyllianB Yahn ◽

JamieE Abato

Keyword(s):

Ischemic Stroke ◽

Vitamin B12 ◽

Stroke Risk ◽

Vitamin B12 Deficiency ◽

B12 Deficiency ◽

Ischemic Stroke Risk

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REPERFUSION RESTORES THE OXYGEN METABOLISM OF SEVERELY ISCHEMIC BRAIN TISSUE IN A CLINICALLY RELEVANT ISCHEMIC STROKE MODEL

10.26226/morressier.5ab8f55fd462b8029238ccac ◽

2018 ◽

Author(s):

Philip Little

Keyword(s):

Ischemic Stroke ◽

Brain Tissue ◽

Oxygen Metabolism ◽

Stroke Model ◽

Ischemic Brain ◽

Ischemic Brain Tissue

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55: The Risk of Vitamin B12 Deficiency is Low after Ileal Orthotopic Bladder Substitution

The Journal of Urology ◽

10.1016/s0022-5347(18)37317-8 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 15-15

Author(s):

Urs E. Studer ◽

Richard Aebischer ◽

Katharina Ochsner ◽

Werner W. Hochreiter

Keyword(s):

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

B12 Deficiency ◽

Bladder Substitution

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Bioavailability of Vitamin B12

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000041 ◽

2010 ◽

Vol 80 (45) ◽

pp. 330-335 ◽

Cited By ~ 28

Author(s):

Lindsay Helen Allen

Keyword(s):

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

The Elderly ◽

Radioactive Isotopes ◽

Animal Source Foods ◽

Dietary Requirements ◽

In Vivo Labeling ◽

B12 Deficiency ◽

Vitamin B12 Malabsorption

Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied to diagnose vitamin B12 malabsorption, including Schillings test, which is now used rarely, but these do not quantify percent bioavailability. Most of the information on B12 bioavailability from foods was collected 40 to 50 years ago, using radioactive isotopes of cobalt to label the corrinoid ring. The data are sparse, and the level of radioactivity required for in vivo labeling of animal tissues can be prohibitive. A newer method under development uses a low dose of radioactivity as 14C-labeled B12, with measurement of the isotope excreted in urine and feces by accelerator mass spectrometry. This test has revealed that the unabsorbed vitamin is degraded in the intestine. The percent bioavailability is inversely proportional to the dose consumed due to saturation of the active absorption process, even within the range of usual intake from foods. This has important implications for the assessment and interpretation of bioavailability values, setting dietary requirements, and interpreting relationships between intake and status of the vitamin.

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Increased monocyte to HDL cholesterol ratio in vitamin B12 deficiency: is it related to cardiometabolic risk?

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000668 ◽

2020 ◽

pp. 1-8

Author(s):

Sanem Kayhan ◽

Nazli Gulsoy Kirnap ◽

Mercan Tastemur

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Uric Acid ◽

Vitamin B12 ◽

Cardiometabolic Risk ◽

Vitamin B12 Deficiency ◽

Left Ventricular ◽

Cardiometabolic Risk Factors ◽

B12 Deficiency ◽

Deficiency Group

Abstract. Vitamin B12 deficiency may have indirect cardiovascular effects in addition to hematological and neuropsychiatric symptoms. It was shown that the monocyte count-to-high density lipoprotein cholesterol (HDL-C) ratio (MHR) is a novel cardiovascular marker. In this study, the aim was to evaluate whether MHR was high in patients with vitamin B12 deficiency and its relationship with cardiometabolic risk factors. The study included 128 patients diagnosed with vitamin B12 deficiency and 93 healthy controls. Patients with vitamin B12 deficiency had significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP), MHR, C-reactive protein (CRP) and uric acid levels compared with the controls (median 139 vs 115 mmHg, p < 0.001; 80 vs 70 mmHg, p < 0.001; 14.2 vs 9.5, p < 0.001; 10.2 vs 4 mg/dl p < 0.001; 6.68 vs 4.8 mg/dl, p < 0.001 respectively). The prevalence of left ventricular hypertrophy was higher in vitamin B12 deficiency group (43.8%) than the control group (8.6%) (p < 0.001). In vitamin B12 deficiency group, a positive correlation was detected between MHR and SBP, CRP and uric acid (p < 0.001 r:0.34, p < 0.001 r:0.30, p < 0.001 r:0.5, respectively) and a significant negative correlation was detected between MHR and T-CHOL, LDL, HDL and B12 (p < 0.001 r: −0.39, p < 0.001 r: −0.34, p < 0.001 r: −0.57, p < 0.04 r: −0.17, respectively). MHR was high in vitamin B12 deficiency group, and correlated with the cardiometabolic risk factors in this group, which were SBP, CRP, uric acid and HDL. In conclusion, MRH, which can be easily calculated in clinical practice, can be a useful marker to assess cardiovascular risk in patients with vitamin B12 deficiency.

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