menaquinone-6 and Brain-Ischemia

Cerebral ischemia/reperfusion (I/R) injury causes cognitive deficits, excitotoxicity, neuroinflammation, oxidative stress and brain edema. Vitamin K2 (Menaquinone 4, MK-4) as a potent antioxidant can be a good candidate to ameliorate I/R consequences. This study focused on the neuroprotective effects of MK-4 for cerebral I/R insult in rat's hippocampus. The rat model of cerebral I/R was generated by transient bilateral common carotid artery occlusion for 20 min. Rats were divided into control, I/R, I/R+DMSO (solvent (1% v/v)) and I/R+MK-4 treated (400 mg/kg, i.p.) groups. Twenty-four hours after I/R injury induction, total brain water content, superoxide dismutase (SOD) activity, nitrate/nitrite concentration and neuronal density were evaluated. In addition to quantify the apoptosis processes, TUNEL staining, as well as expression level of Bax and Bcl2, were assessed. To evaluate astrogliosis and induced neurotoxicity by I/R GFAP and GLT-1 mRNA expression level were quantified. Furthermore, pro-inflammatory cytokines including IL-1β, IL-6 and TNF-α were measured. Seven days post I/R, behavioral analysis to quantify cognitive function, as well as Nissl staining for surviving neuronal evaluation, were conducted. The findings indicated that administration of MK-4 following I/R injury improved anxiety-like behavior, short term and spatial learning and memory impairment induced by I/R. Also, MK-4 was able to diminish the increased total brain water content, apoptotic cell density, Bax/ Bcl2 ratio and GFAP mRNA expression following I/R. In addition, the high level of nitrate/nitrite, IL-6, IL-1β and TNF-α induced by I/R was reduced after MK-4 administration. However, MK-4 promotes the level of SOD activity and GLT-1 mRNA expression in I/R rat model. The findings demonstrated that MK-4 can rescue transient global cerebral I/R consequences via its anti-inflammatory and anti-oxidative stress features. MK-4 administration ameliorates neuroinflammation, neurotoxicity and neuronal cell death processes and leads to neuroprotection.

Topics: Animals; Apoptosis; Brain; Brain Ischemia; Excitatory Amino Acid Transporter 2; Glial Fibrillary Acidic Protein; Interleukin-1beta; Interleukin-6; Male; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion Injury; Spatial Learning; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Vitamin K 2

Dietary vitamin K intake is thought to decrease the risk of cardiovascular disease (CVD) by reducing vascular calcification, although vitamin K is also involved in coagulation. Studies investigating the association between phylloquinone intake and risk of stroke are scarce, and the relation with menaquinones has not been investigated to date.. We investigated the association between intake of phylloquinone and menaquinones and stroke in a prospective cohort of 35,476 healthy subjects. Information on occurrence of stroke was obtained by linkage to national registries, and stroke was further specified into ischemic and hemorrhagic stroke. Vitamin K intake was estimated using a validated food-frequency questionnaire. Multivariate Cox proportional hazards models adjusted for cardiovascular risk factors, lifestyle, and other dietary factors were used to estimate the associations. During a follow-up of 12.1 ± 2.1 years, 580 incident cases of stroke were identified, 163 of which were hemorrhagic and 324 were ischemic. Phylloquinone intake was not associated with risk of stroke with a hazard ratio (HR) of 1.09 (95% CI: 0.85 to 1.40, P(trend) 0.41) for the highest versus lowest quartile. For intake of menaquinones similar results were found, with an HR(Q4 versus Q1) of 0.99 (95% CI: 0.75 to 1.29, P(trend) 0.82). When specifying hemorrhagic and ischemic stroke or menaquinone subtypes, no significant associations were detected.. In our study, neither dietary phylloquinone nor dietary menaquinones intake were associated with stroke risk.

Topics: Adult; Aged; Brain Ischemia; Diet; Female; Humans; Intracranial Hemorrhages; Linear Models; Male; Middle Aged; Multivariate Analysis; Netherlands; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Stroke; Surveys and Questionnaires; Vitamin K 1; Vitamin K 2; Young Adult