Phytosome Loading the Combined Extract of Mulberry Fruit and Ginger Protects against Cerebral Ischemia in Metabolic Syndrome Rats.

The prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPARγ expression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF-κB, TNFα, and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPARγ expression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPARγ resulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential.

Coenzyme Q10 supplementation in acute ischemic stroke: Is it beneficial in short-term administration?

Backgrounds and aims: Clinical studies demonstrated that the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapeutic agent in several neurological diseases such as Parkinson disease (PD), Huntington disease (HD), and migraine. The purpose of this study is to investigate oxidative stress effects, antioxidant enzymes activity, neuroinflammatory markers levels, and neurological outcome in acute ischemic stroke (AIS) patients following administration of CoQ10 (300 mg/day). Methods: Patients with AIS (n = 60) were randomly assigned to a placebo group (wheat starch, n = 30) or CoQ10-supplemented group (300 mg/day, n = 30). The intervention was administered for 4 weeks. Serum CoQ10 concentration, malondialdehyde (MDA), superoxide dismutase (SOD) activity, glial fibrillary acidic protein (GFAP) levels as primary outcomes and National Institute of Health Stroke Scale (NIHSS), Modified Ranking Scale (MRS), and Mini-Mental State Examination (MMSE) as secondary outcome were measured at the both beginning and end of the study. Results: Forty-four subjects with AIS completed the intervention study. A significant increase in CoQ10 level was observed in the supplement-treated group compared with placebo group (mean difference = 26.05 ± 26.63 ng/ml, 14.12 ± 14.69 ng/ml, respectively; P = 0.01), moreover CoQ10 supplementation improved NIHSS and MMSE scores significantly (P = 0.05, P = 0.03 respectively). but there were no statistically significant differences in MRS score, MDA, SOD, and GFAP levels between the two groups. Conclusions: CoQ10 probably due to low dose and short duration of supplementation, no favorable effects on MDA level, SOD activity and GFAP level.

Early Motor-Behavioral Outcome of Ischemic Stroke with Ketogenic Diet Preconditioning: Interventional Animal Study.

BACKGROUND: Cerebral stroke, with ischemic stroke being its most common type, is the leading cause of chronic disability. The ketogenic diet has been used for treating seizures for centuries and has been considered to be a treatment for other neurologic diseases in recent years. The goal of this study is to evaluate the effects of ketogenic diet preconditioning on the early motor-behavior outcome of rats with induced cerebral ischemic stroke. METHODS: Twenty-four rats were surveyed in 3 groups of Main, Control, and Sham. The Main group received a ketogenic diet plus medium chain triglyceride oil starting 3 days prior to stroke induction, while the other 2 groups took a normal diet. Subsequently, Endothelin-1 was injected stereotactically near the middle cerebral artery to induce an ischemic stroke in the Main and Control group. Normal saline was injected to the members of the Sham group with the same technique. The motor-behavior functions of the rats were compared between 3 groups using adjusting step, beam, and cylinder tests. RESULTS: After stroke induction, rats on ketogenic diet were able to adjust their steps more efficiently, moved faster on the beam, and used their hands more symmetrically in the transparent cylinder in relation to the rats in the Control group. CONCLUSION: It seems that ketogenic diet preconditioning improves the early motor-behavioral outcome of ischemic stroke.

Therapeutic effects of dietary intervention on neuroinflammation and brain metabolism in a rat model of photothrombotic stroke.

INTRODUCTION: A possible target for stroke management is modulation of neuroinflammation. Evidence suggests that food components may exert anti-inflammatory properties and thus may reduce stroke-induced brain damage. AIM: To investigate the efficacy of a diet, containing anti-inflammatory ingredients, as treatment for focal ischemic brain damage induced by photothrombotic stroke in the somatosensory cortex of rats. RESULTS: Brain lesions were surrounded by strong astrogliosis on both day 7 and day 21 after stroke and were accompanied by a trend toward globally decreased glucose metabolism on day 7. The investigational diet applied 2 weeks before the ischemia did not affect astrocyte activation on day 7, but reduced it at day 21. The investigational diet applied immediately after the ischemia, increased astrocyte activation on day 7 and completely reversed this effect on day 21. Moreover, postischemic intervention increased glucose metabolism in somatosensory cortex ipsilateral to the lesion on day 7. CONCLUSION: This study reveals potentially beneficial effects of a diet containing elevated amounts of anti-inflammatory nutrients on the recovery from ischemic brain damage. Therefore, dietary intervention can be considered as an adjuvant therapy for recovery from this brain pathology.

Impact of Early High-protein Diet on Neurofunctional Recovery in Rats with Ischemic Stroke.

BACKGROUND Ischemic stroke, featuring high incidence, morbidity, and mortality, is one of the three major diseases troubling human beings. The purpose of the study was to examine the impact of early high-protein diet on neurofunctional recovery in rats with ischemic stroke as well as their cerebral infarct areas and molecular expressions of oxidative stress. MATERIAL AND METHODS The middle cerebral artery occlusion model (MCAO) was established, and 48 adult, male Sprague Dawley (SD) rats of clean grade aged seven to eight months (250-280 g body weight) were randomized into four groups: the MCAO group with high-protein diet (MH), the MCAO group with standard-protein diet (MS), the sham group with high-protein diet (SH), and the sham group with standard-protein diet (SS). High-protein diet intervention started on the first day of the surgery, and the rats' body weights and their neurological deficit scores were measured on each postoperative day while the scores of motors coordination and balance ability were recorded every other day. In addition, their cerebral infant areas and the molecular expressions of oxidative stress injuries were detected as well. RESULTS Compared to the MS group, the rats in the MH group gained faster weight growth (p<0.05), presented significantly lower neurological impairment scores (p<0.05), remarkably improved motor coordination and balance ability (p<0.05) as well as showed smaller cerebral infarct areas (p<0.05), increased expression of SOD (superoxide dismutase), and reduced expressions of MDA (malondialdehyde) and iNOS (inducible nitric oxide synthase). However, there was no significant difference between the SS group and the SH group (p>0.05). CONCLUSIONS Early high-protein diet facilitates the recovery of body weights and neurological functions as well the reduction of the cerebral infarct areas of rats, thus alleviating ischemic stroke-caused oxidative stress injuries.

Effect of a multinutrient intervention after ischemic stroke in female C57Bl/6 mice.

Stroke can affect females very differently from males, and therefore preclinical research on underlying mechanisms and the effects of interventions should not be restricted to male subjects, and treatment strategies for stroke should be tailored to benefit both sexes. Previously, we demonstrated that a multinutrient intervention (Fortasyn) improved impairments after ischemic stroke induction in male C57Bl/6 mice, but the therapeutic potential of this dietary treatment remained to be investigated in females. We now induced a transient middle cerebral artery occlusion (tMCAo) in C57Bl/6 female mice and immediately after surgery switched to either Fortasyn or an isocaloric Control diet. The stroke females performed several behavioral and motor tasks before and after tMCAo and were scanned in an 11.7 Tesla magnetic resonance imaging (MRI) scanner to assess brain perfusion, integrity, and functional connectivity. To assess brain plasticity, inflammation, and vascular integrity, immunohistochemistry was performed after killing of the mice. We found that the multinutrient intervention had diverse effects on the stroke-induced impairments in females. Similar to previous observations in male stroke mice, brain integrity, sensorimotor integration and neurogenesis benefitted from Fortasyn, but impairments in activity and motor skills were not improved in female stroke mice. Overall, Fortasyn effects in the female stroke mice seem more modest in comparison to previously investigated male stroke mice. We suggest that with further optimization of treatment protocols more information on the efficacy of specific interventions in stroked females can be gathered. This in turn will help with the development of (gender-specific) treatment regimens for cerebrovascular diseases such as stroke. This article is part of the Special Issue "Vascular Dementia".

[Thrombolytic therapy of ischemic stroke]. / Tromboliticheskaia terapiia ishemicheskogo insul'ta.

Reperfusion therapy is one of the main treatment strategies of ischemic stroke. The first studies of the efficacy of thrombolytic medications started form the use of streptokinase and fibrinolysin in patients with ischemic stroke in late 50 - early 60 of the XX century in the United States, Soviet Union, and Western Europe. After the development of recombinant tissue plasminogen activator, thrombolysis became one of the main methods of reperfusion in patients with acute ischemic stroke, acute myocardial infarction, or other acute vascular thrombotic events. Later, modified variants of tissue plasminogen activator with prolonged clearance time, high fibrin-selectivity, and bolus delivery were introduced. Another group of thrombolytic agents includes derivatives of flora and fauna - external plasminogen activators, of which streptokinase, staphylokinase, and desmoteplase are most common drugs. These medications are not a structural part of the human organism, and overcoming of immunogenicity while preserving fibrinolytic activity and fibrin specificity is one of the main tasks in applying them in clinical practice.

Supplementation with different teas from Camellia sinensis prevents memory deficits and hippocampus oxidative stress in ischemia-reperfusion.

Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis.

Effect of Vitamin D and calcium supplementation on ischaemic stroke outcome: a randomised controlled open-label trial.

BACKGROUND AND AIMS: Vitamin D deficiency is a common problem in stroke survivors. Observational studies have reported an association of low vitamin D levels with greater stroke severity, poststroke mortality and functional disability. Randomised clinical trials are lacking. We sought to assess the effect of calcium and vitamin D supplementation in ischaemic stroke survivors with vitamin D deficiency/insufficiency on disability/mortality outcomes. METHODS: In this randomised controlled open-label trial, 73 patients of acute ischaemic stroke were screened for serum 25 hydroxy Vitamin D (25(OH)D) levels. A total of 53 patients with baseline 25(OH)D <75 nmol/L were randomised into two arms. One received vitamin D and calcium supplementation along with usual care (n=25) and the other received usual care alone (n=28). Primary outcome was the proportion of patients achieving a good outcome [modified Rankin Scale score 0-2] at 6 months and all cause mortality at 6 months. RESULTS: The age (mean±SD) of participants was 60.4±11.3 years, 69.8% were males. The proportion of patients achieving good outcome was higher in the intervention arm (Adjusted OR 1.9, 95% CI 0.6-6.4; P=.31). The survival probability was greater in the intervention arm (83.8%, CI 62.4-93.6) as compared with the control arm (59.5%, CI 38.8-75.2; P=.049) with adjusted Hazard ratio (HR) of 0.26 (95% CI 0.08-0.9; P=.03). CONCLUSIONS: This is the first randomised controlled study assessing the effect of vitamin D and calcium supplementation on ischaemic stroke outcomes and points towards a potential benefit. Findings need to be validated by a larger trial.

Alpha-linolenic acid given as enteral or parenteral nutritional intervention against sensorimotor and cognitive deficits in a mouse model of ischemic stroke.

Stroke is a leading cause of disability and death worldwide. Numerous therapeutics applied acutely after stroke have failed to improve long-term clinical outcomes. An emerging direction is nutritional intervention with omega-3 polyunsaturated fatty acids acting as disease-modifying factors and targeting post-stroke disabilities. Our previous studies demonstrated that the omega-3 precursor, alpha-linolenic acid (ALA) administrated by injections or dietary supplementation reduces stroke damage by direct neuroprotection, and triggering brain artery vasodilatation and neuroplasticity. Successful translation of putative therapies will depend on demonstration of robust efficacy on common deficits resulting from stroke like loss of motor control and memory/learning. This study evaluated the value of ALA as adjunctive therapy for stroke recovery by comparing whether oral or intravenous supplementation of ALA best support recovery from ischemia. Motor and cognitive deficits were assessed using rotarod, pole and Morris water maze tests. ALA supplementation in diet was better than intravenous treatment in improving motor coordination, but this improvement was not due to a neuroprotective effect since infarct size was not reduced. Both types of ALA supplementation improved spatial learning and memory after stroke. This cognitive improvement correlated with higher survival of hippocampal neurons. These results support clinical investigation establishing therapeutic plans using ALA supplementation.

[The use of cytoflavin in reperfusion in ischemic stroke]. / Primenenie tsitoflavina pri reperfuzionnoi terapii ishemicheskogo insul'ta.

OBJECTIVE: to study the efficacy of cytoflavin in thrombolytic treatment of patients with acute ischemic stroke (IS). MATERIAL AND METHODS: Fifty-five patients in the acute stage of IS were examined. The National Institutes of Health Stroke scale (NIHSS), the Rankin scale and the Barthel index of activities of daily living were used. Depending on the scheme of treatment, patients were divided into 2 groups: the first (basic) group included 29 patients who received cytoflavin immediately after thrombolytic therapy. The control group (26 patients) received basic vascular and neuroprotective treatment. RESULTS AND CONCLUSION: The marked reduction in the severity of neurological symptoms to the 10th day of treatment and higher probability of a successful outcome were noted in the basic group compared to the controls. There was an improvement of functional activities according to the Rankin scale and of activities of daily living assessed by the Barthel index, with scores "moderate dependence" in the basic group and "severe dependence" in the control group. The inclusion of cytoflavin in the treatment scheme of patients with acute IS increased the efficacy of treatment.

Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke: Results From 2 Prospective Cohorts.

BACKGROUND AND PURPOSE: High adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower risk of hypertension, the major risk factor for stroke. We examined whether adherence to the DASH diet is inversely associated with the incidence of stroke. METHODS: The study population comprised 74 404 men and women (45-83 years of age), without stroke at baseline, from the Cohort of Swedish Men and the Swedish Mammography Cohort. Diet was assessed with a food-frequency questionnaire. A modified DASH diet score was created based on consumption of vegetables, fruits, legumes and nuts, whole grains, low-fat dairy, red meat and processed meat, and sweetened beverages. Stroke cases were identified through linkage to the Swedish National Patient and Cause of Death Registers. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards regression model. RESULTS: During 882 727 person-years (mean, 11.9 years) of follow-up, 3896 ischemic strokes, 560 intracerebral hemorrhages, and 176 subarachnoid hemorrhages were ascertained. The modified DASH diet score was statistically significantly inversely associated with the risk of ischemic stroke (P for trend=0.002), with a multivariable relative risk of 0.86 (95% confidence interval, 0.78-0.94) for the highest versus the lowest quartile of the score. The modified DASH diet score was nonsignificantly inversely associated with intracerebral hemorrhage (corresponding relative risk=0.81; 95% confidence interval, 0.63-1.05) but was not associated with subarachnoid hemorrhage. CONCLUSIONS: These findings indicate that high adherence to the DASH diet is associated with a reduced risk of ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711 for the Swedish Mammography Cohort and the Cohort of Swedish Men, respectively.

Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis.

BACKGROUND: The effects of green tea intake on risk of cardiovascular disease (CVD) have not been well-defined. The aim of this meta-analysis was to evaluate the association between green tea consumption, CVD, and ischemic related diseases. METHODS: All observational studies and randomized trials that were published through October 2014 and that examined the association between green tea consumption and risk of cardiovascular and ischemic related diseases as the primary outcome were included in this meta-analysis. The quality of the included studies was evaluated according to the Cochrane Handbook 5.0.2 quality evaluation criteria. RESULTS: A total of 9 studies including 259,267 individuals were included in the meta-analysis. The results showed that those who didn't consume green tea had higher risks of CVD (OR=1.19, 95% CI: 1.09-1.29), intracerebral hemorrhage (OR=1.24, 95% CI: 1.03-1.49), and cerebral infarction (OR=1.15, 95% CI: 1.01-1.30) compared to <1 cup green tea per day. Those who drank 1-3 cups of green tea per day had a reduced risk of myocardial infarction (OR=0.81, 95% CI: 0.67-0.98) and stroke (OR=0.64, 95% CI: 0.47-0.86) compared to those who drank <1 cup/day. Similarly, those who drank ≥4 cups/day had a reduced risk of myocardial infarction compared to those who drank <1 cup/day (OR=0.68, 95% CI: 0.56-0.84). Those who consumed ≥10 cups/day of green tea were also shown to have lower LDL compared to the <3 cups/day group (MD=-0.90, 95% CI: -0.95 to -0.85). CONCLUSIONS: Our meta-analysis provides evidence that consumption of green tea is associated with favorable outcomes with respect to risk of cardiovascular and ischemic related diseases.

[The efficacy of low calorie diet therapy in patients with arterial hypertension and chronic cerebral ischemia].

OBJECTIVE: To evaluate an impact of low calorie diet therapy (LCDT) on cerebral hemodynamics, cognitive functions and quality-of-life of patients with arterial hypertension and chronic cerebral ischemia. MATERIAL AND METHODS: The main group consisted of 22 patients, 16 women and 6 men (mean age 54.4±2.4 years), assigned to the diet. The comparison group included 20 patients, 12 women and 8 men (mean age 55.6±1,0 years), who received standard antihypertensive treatment. The results of Doppler ultrasound of cerebral arteries, cognitive functions and quality-of-life were assessed after 6 months of treatment. RESULTS AND CONCLUSION: A positive effect of LCDT on the cerebral hemodynamics, cognitive functions and quality-of-life indices maintained for 6 months. The efficacy of LCDT was comparable to that of standard treatment in the comparison group.

Dietary fats significantly influence the survival of penumbral neurons in a rat model of chronic ischemic by modifying lipid mediators, inflammatory biomarkers, NOS production, and redox-dependent apoptotic signals.

OBJECTIVE: Brain stroke is the third most important cause of death in developed countries. We studied the effect of different dietary lipids on the outcome of a permanent ischemic stroke rat model. METHODS: Wistar rats were fed diets containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed) for 35 d. Stroke was induced by permanent middle cerebral artery occlusion. Coronal slices from ischemic brains and sham-operated animals were supravitally stained. Penumbra and core volumes were calculated by image digitalization after 24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were prepared from different zones and analyzed by redox status, inflammatory markers, ceramide, and arachidonate content, phospholipase A2, NOS, and proteases. RESULTS: Soybean (S) and G diets were mainly prooxidative and proinflammatory by increasing the liberation of arachidonate and its transformation into prostaglandins. O was protective in terms of redox homeostatic balance, minor increases in lipid and protein damage, conservation of reduced glutathione, protective activation of NOS in penumbra, and net ratio of anti-to proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was less activated by O than by any other diet. CONCLUSION: Dietary lipids modulate NOS and PLA2 activities, ceramide production, and glutathione import into the mitochondrial matrix, finally determining the activation of the two main protease systems involved in programmed cell death. Olive oil appears to be a biological source for the isolation of protective agents that block the expansion of brain core at the expense of penumbral neurons.

Reduced severity of ischemic stroke and improvement of mitochondrial function after dietary treatment with the anaplerotic substance triheptanoin.

Triheptanoin, an oily substance, consists of glycerol bound to three molecules of heptanoic acid, a C7 odd-chain fatty acid. A triheptanoin-rich diet has anaplerotic effects because heptanoate metabolism yields succinate which delivers substrates to the Krebs cycle. While previous studies on the effects of triheptanoin focused on metabolic disorders and epilepsy, we investigated triheptanoin's effect on ischemic stroke. Mice were fed a triheptanoin-enriched diet for 14days; controls received soybean oil. Only mice fed triheptanoin had measurable quantities of odd-numbered fatty acids in the plasma and brain. Transient ischemia was induced in the brain by occlusion of the middle cerebral artery (MCAO) for 60min. One day later, mice were tested for neurological function (chimney, rotarod and corner tests) which was found to be better preserved in the triheptanoin group. Microdialysis demonstrated that the strong, neurotoxic increase of extracellular glutamate, which was observed in the mouse striatum during MCAO, was strongly reduced in triheptanoin-fed mice while glucose levels were not affected. Triheptanoin diet reduced the infarct area in stroked mice by about 40%. In ex vivo-experiments with isolated mitochondria, ischemia was found to cause a reduction of mitochondrial respiratory activity. This reduction was attenuated by triheptanoin diet in complex II and IV. In parallel measurements, ATP levels and mitochondrial membrane potential were reduced in control animals but were preserved in triheptanoin-fed mice. We conclude that triheptanoin-fed mice which sustained an experimental stroke had a significantly improved neurological outcome. This beneficial effect is apparently due to an improvement of mitochondrial function and preservation of the cellular energy state. Our findings identify triheptanoin as a promising new dietary agent for neuroprotection.

Calorie restriction attenuates cerebral ischemic injury via increasing SIRT1 synthesis in the rat.

Caloric restriction (CR) has been shown to have several health benefits and provides protection against type 2 diabetes, neurodegenerative and cerebral vascular diseases. It reduces the brain infarct size and promotes neurological functional recovery after cerebral ischemia. Sirtuin 1 (SIRT1) plays an important role in the biological effects induced by CR. This study investigated the role of SIRT1 in ischemic tolerance in the brain induced by CR. Sprague drawly rats were divided into two groups based on food intake. Ad libitum (AL) group was fed with normal diet while the CR group received 60% calories compared to AL. All animals were subjected to a middle cerebral artery occlusion for 90 min. Results showed the neurological function score of CR group was higher and the brain infarct volume was markedly reduced in CR group compared to AL group at 24h after reperfusion (p < 0.05). CR increased the synthesis of SIRT1 significantly (p < 0.05), and ameliorated the down regulation of SIRT1 expression at 6 and 12h after middle cerebral artery occlusion (p < 0.05, p < 0 .01, respectively). Knockdown of SIRT1 by siRNA in vivo reversed the neuroprotective effect of CR. From this study, we deduce that CR induces brain ischemic tolerance on rats via increasing the synthesis of SIRT1.

Dietary Sutherlandia and elderberry mitigate cerebral ischemia-induced neuronal damage and attenuate p47phox and phospho-ERK1/2 expression in microglial cells.

Sutherlandia (Sutherlandia frutescens) and elderberry (Sambucus spp.) are used to promote health and for treatment of a number of ailments. Although studies with cultured cells have demonstrated antioxidative and anti-inflammatory properties of these botanicals, little is known about their ability to mitigate brain injury. In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion (I/R) revealed significant reduction in neuronal cell death in both dietary groups. Immunohistochemical staining for ionized calcium-binding adapter molecule-1 demonstrated pronounced activation of microglia in the hippocampus and striatum in the ischemic brains 3 days after I/R, and microglial activation was significantly reduced in animals fed supplemented diets. Mitigation of microglial activation by the supplements was further supported by the decrease in expression of p47phox, a cytosolic subunit of NADPH oxidase, and phospho-ERK1/2, a mitogen-activated protein kinase known to mediate a number of cytoplasmic processes including oxidative stress and neuroinflammatory responses. These results demonstrate neuroprotective effect of Sutherlandia and American elderberry botanicals against oxidative and inflammatory responses to cerebral I/R.

Anti-oxidative nutrient-rich diet protects against acute ischemic brain damage in rats.

We evaluated the neuroprotective effects of an anti-oxidative nutrient rich enteral diet (AO diet) that contained rich polyphenols (catechins and proanthocyanidins) and many other anti-oxidative ingredients. Wistar rats were treated with either vehicle, normal AO diet (containing 100kcal/100mL, catechin 38.75mg/100mL and proanthocyanidin 19mg/100mL, 1mL/day), or high AO diet (containing 10 times the polyphenols of the normal AO diet) for 14 days, and were subjected to 90min of transient middle cerebral artery occlusion. The AO diet improved motor function, reduced cerebral infarction volume, and decreased both peroxidative markers such as 4-hydroxynonenal, advanced glycation end products, 8-hydroxy-2-deoxyguanosine and inflammatory markers such as monocyte chemotactic protein-1, ionized calcium-binding adapter molecule-1, and tumor necrosis factor-α. Our study has shown that an AO diet has neuroprotective effects through both anti-oxidative and anti-inflammatory mechanisms, indicating that nutritional control with polyphenols could be useful for patients with acute ischemic stroke.

Garlic intake is an independent predictor of endothelial function in patients with ischemic stroke.

OBJECTIVES: To investigate the effects of garlic on endothelial function in patients with ischemic stroke (ISS). DESIGN: Cross-sectional study. PARTICIPANTS: 125 Chinese patients with prior ISS due to athero-thrombotic disease were recruited from the outpatient clinics during July 2005 to December 2006. MEASUREMENTS: Daily allium vegetable intake (including garlic, onions, Chinese chives and shallots) was ascertained by means of a validated food frequency questionnaire for Chinese and brachial artery flow-mediated dilatation (FMD) was measured using high-resolution ultrasound in all subjects. RESULTS: The mean age of the study population was 65.9±11.1 years and 69% were males. Mean allium vegetable intake and garlic intake of the study population was 7.5±12.7g/day and 2.9±8.8g/day respectively. Their mean FMD was 2.6±2.3%. Daily intake of total allium vegetable (r=0.36, P<0.01) and garlic (r=0.34, P<0.01) significantly correlated with FMD. Using the median daily allium intake as cut-off (3.37g/day), patients with a low allium intake <3.37g/day was noted to have a lower FMD compared to those with a normal allium intake (2.1±2.1% versus 3.0±2.4%, P<0.05). After adjusting for confounding factors, multi-variate analysis identified that daily allium vegetable (B=0.05, 95% confidence interval: 0.02, 0.09, P<0.01) and garlic (B=0.07, 95% confidence interval: 0.02, 0.12, P<0.01) intake, but not onions, Chinese chives and shallots were independent predictors for changes in FMD in patients with ISS. CONCLUSIONS: Daily garlic intake is an independent predictor of endothelial function in patients with ISS and may play a role in the secondary prevention of atherosclerotic events.