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The mice were then transferred to a stereotaxic apparatus (Harvard Apparatus) and maintained at 2–2.5% isoflurane. Tear gel was used to prevent their eyes from drying out while anesthetized and 0.03 mg/kg of buprenorphine and 1 mL of saline were administered subcutaneously. After anesthetization, the mice had the top of their heads shaved and disinfected. Using the photothrombosis model of ischemic stroke damage, the mice were anesthetized with 4–5% isoflurane in oxygen. This study adds an understanding of the mechanisms through which a dietary vitamin B12 deficiency changes the female brain and behavior using a mouse model system. Stroke outcomes in women are not well understood. The literature shows a clear link between a dietary deficiency in vitamin B12 and an increased risk for ischemic stroke and worse outcome, but the mechanisms remain unknown. The impact of vitamin B12 deficiency after stroke on mitochondrial function requires further investigation. Mitochondria are a major contributor to the development of apoptotic and necrotic cell death after ischemic stroke. Vitamin B12 plays an essential role in mitochondrial energy production and cellular function. The literature demonstrates that patients with a vitamin B12 deficiency and hyperhomocysteinemia during an ischemic stroke have been reported to have worse outcomes. A vitamin B12 deficiency results in increased levels of homocysteine, which is a risk factor for stroke. Vitamin B12 is a component of one-carbon (1C) metabolism, which is a network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics, and plays an essential role in the regulation of cell proliferation, stress resistance, and embryo development. Another aim of this paper is to bridge this gap and increase insight into the female-specific stroke mechanisms and treatment. Assessing these differences and strengthening female treatment is lost in the lack of female focus in preclinical studies. This approach is taken despite stroke frequency and outcomes in female mice and human participants changing depending on age, menopause, and other female-specific biological factors that are not applicable in males.
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This makes clinical pharmaceutical findings favor better outcomes in males. Over 90% of preclinical studies use strictly male mice, whereas all clinical studies use equal numbers of male and female participants. Women have more risk factors and worse outcomes than men with CVD One of the many reasons these problems exist is that preclinical studies are targeted towards males. Ĭardiovascular disease (CVD) is the leading cause of death among men and women. Approximately 20% of older adults (>60 years old) have a vitamin B12 deficiency, making it of high concern to this population. For example, a vitamin B12 deficiency is a well-established risk factor for stroke and worse stroke outcomes. Nutrition is a modifiable risk factor for stroke. Many factors contribute to stroke risk and outcomes, making it highly multifactorial. The blockage results in reduced oxygen and energy supply to the brain, causing severe disability and death. It is caused by blockage of arterioles leading to portions of the brain. Ischemic stroke is the most common form of stroke. Currently, stroke is prevalent and detrimental to elderly populations (>65 years old). Stroke is among the leading causes of death globally and its prevalence as a major health concern is predicted to increase as the global population ages and the demographics of populations change. impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue. Motor function after stroke was impaired in vit. The analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. The cecum tissue pathway analysis showed dysfunction in B12 transport. animals had larger damage volume in brain tissue and more apoptosis. animals had increased levels of total homocysteine in plasma and liver, and choline levels were also increased in the liver. After damage, motor function was measured, the animals were euthanized, and tissues were collected for analysis. diet for 4 weeks, after which an ischemic stroke was induced in the sensorimotor cortex. Eighteen-month-old females were put on a control or vit. on stroke outcome and mechanisms using aged female mice. changes the brain requires further investigation. results in worse outcome after stroke, and the mechanisms through which a vit. Clinical studies have reported that a vit. B12 def.) is common in the elderly, because of changes in metabolism.