In the last few decades, perturbation in methyl-group and homocysteine (Hcy) balance have emerged as independent risk factors in a number of pathological conditions including neurodegenerative disease, cardiovascular dysfunction, cancer development, autoimmune disease, and kidney disease. Recent studies report Hcy to be a newly recognized risk factor for osteoporosis. Elevated Hcy levels are known to modulate osteoclastgenesis by causing detrimental effects on bone via oxidative stress induced metalloproteinase-mediated extracellular matrix degradation and decrease in bone blood flow. Evidence from previous studies also suggests that the decreased chondrocytes mediated bone mineralization in chick limb-bud mesenchymal cells and during the gestational period of ossification in rat model. However, Hcy imbalance and its role in bone loss, regression in vascular invasion, and osteoporosis, are not clearly understood. More investigations are required to explore the complex interplay between Hcy imbalance and onset of bone disease progression. This article reviews the current body of knowledge on regulation of Hcy mediated oxidative stress and its role in bone remodeling, vascular blood flow and progression of bone disease.

No abstract

Methionine is an essential amino acid found in rich quantities in average American diet such as meats, fish and eggs. Excessive consumption of such food often exceeds the normal requirement of the methionine in our body; which found to be related to the development of neurodegenerative disorders. However, the mechanistic pathways of methionine's influence on the brain are unclear. The present study is focus on the effects of high methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet on the dysfunction of neuronal and vascular specific markers in the brain. C57BL6/J male mice (8-10 week old) were fed with HM-LF-LV diet for a 6 week period. Cognitive function of mice was determine by measuring short-term memory using a Novel Object Recognition test (NORT). Neuronal dysfunction were evaluate by measuring the levels of Neuronal nuclear antigen (NeuN), Neuron-specific-enolase (NSE) and Fluoro-jade C(FJC) fluorescence; while cerebrovascular disruption were evaluate by assessing levels of endothelial junction proteins Vascular Endothelial-Cadherin (VE-Cadherin) and Claudin-5 in harvested brain tissue. Cerebrovascular permeability was assess by evaluating microvascular leakage of fluorescently labeled albumin in vivo. Endothelial and Neuronal Nitric Oxide Synthase (eNOS, nNOS) regulation and vascular inflammation (ICAM: intercellular adhesion molecules) were also evaluate in brain tissue. All assessments were conduct at weekly intervals throughout the study duration. NORT showed a significant temporal decrease in short-term memory of mice fed on HM-LF-LV diet for 6 weeks compared to the wild-type control group. Our experimental data showed that neuronal dysfunction (decreased NeuN levels and increased FJC positive neurons in brain) was more prominent in HM-LF-LV diet fed mice compared to normal diet fed control mice. In experimental mice, cerebrovascular disruption was found to be elevated as evident from increased pial venular permeability (microvascular leakage) and decreased in VE-Cadherin expression compared to control. Slight decrease in nNOS and increase in eNOS in experimental mice suggest a trend towards the decrease in potential for neuronal development due to the long-term HM-LF-LV diet fed. Collectively, our results suggest that a diet containing high methionine, low folate and low vitamin B6/B12 results in increased neuronal degeneration and vascular dysfunction, leading to short-term memory loss. Interestingly, significant neuronal damage precedes vascular dysfunction.

Glycerol rhizotomy was originally described as an initial surgical treatment for trigeminal neuralgia after the failure of medical therapy. Here we describe its use as a salvage procedure, typically after failure of multiple other modalities including microvascular decompression, stereotactic radiosurgery, and/or other percutaneous procedures. Foramen ovale cannulation as a "salvage procedure" may be complicated by lack of cerebrospinal fluid (CSF) return despite adequate cannulation of the foramen ovale, making conventional fluoroscopic confirmation of adequate needle placement less certain. In this article, we describe the application of intraoperative CT, fused with high-resolution preoperative CT/MRI for neuronavigation to accurately cannulate the foramen ovale and Meckel's cave for glycerol rhizotomy. Intraoperative CT, again fused with high-resolution preoperative CT and MRI studies, was then used to confirm accurate trajectory through the foramen ovale and the adequate location of the needle tip in Meckel's cave before injecting glycerol. We present our initial experience with 14 patients who underwent glycerol rhizotomy by these techniques depending on intraoperative CT. It appears that intraoperative CT-guided neuronavigation provides a practical, reliable, and accurate route to the foramen ovale and aids in the confirmation of adequate needle placement even when there is a lack of CSF return. These methods may be especially useful for difficult cannulations typical in salvage procedures. In an era of feasible intraoperative guidance, with advanced stereotactic planning software allowing the fusion of intraoperative CT with high-resolution preoperative CT and MRI datasets, these techniques can be applied to foramen ovale cannulation for glycerol rhizotomy without major modification.