Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity

Although inflammatory responses increase stroke severity, the role of immune cells specific for central nervous system (CNS) antigens remains controversial. Disruption of the blood–brain barrier (BBB) during stroke allows CNS antigens to leak into the peripheral circulation and enhances access of circulating leukocytes to the brain, including those specific for CNS antigens such as myelin oligodendrocyte glycoprotein (MOG) that can induce experimental autoimmune encephalomyelitis (EAE). We here demonstrate for the first time that myelin reactive splenocytes specific for MOG transferred into severe combined immunodeficient (SCID) mice can migrate into the infarct hemisphere of recipients subjected to 60 min middle cerebral artery occlusion (MCAO) and 96 h reperfusion; moreover these cells exacerbate infarct volume and worsen neurological deficits compared to animals transferred with na?ve splenocytes. These findings indicate that autoimmunity in the CNS can exert detrimental injury on brain cells and worsen the damage from ischemic stroke.     

Longitudinal assessment of pigtailed macaque lower genital tract microbiota by pyrosequencing reveals dissimilarity to the genital microbiota of healthy humans

Abstract Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.     

A platelet target for venous thrombosis? P2Y1 deletion or antagonism protects mice from vena cava thrombosis

A role for platelets in the pathogenesis of venous thrombosis was suggested by clinical and preclinical studies. However, examination of the platelet receptor, P2Y1, in this area has been limited. The goal of the current study was to examine effects of P2Y1 deletion, or selective antagonism with MRS2500, in oxidative venous thrombosis in mice. The P2Y12 antagonist, clopidogrel, was included as a reference agent. Anesthetized C57BL/6 or genetically modified mice underwent 3.5 or 5 % FeCl(3)-induced vena cava thrombosis. Pharmacokinetic properties of MRS2500 were defined for dose selection. Platelet aggregation and renal or tail bleeding times (BT) were measured to put antithrombotic effects into perspective. P2Y1 deletion significantly reduced (p < 0.001) venous thrombus weight by 74 % in 3.5 % FeCl(3) injury compared to P2Y1(+/+) littermates. MRS2500 (2 mg/kg, i.v.) significantly decreased (p < 0.001) thrombus weight 64 % in C57BL/6 mice. In the more severe 5 % FeCl(3)-induced injury model, thrombus weight significantly (p < 0.001) decreased 68 % in P2Y1(-/-) mice versus P2Y1(+/+) mice, and MRS2500 (2 mg/kg) was also beneficial (54 % decrease, p < 0.01). Renal BT doubled in P2Y1(-/-) versus P2Y1(+/+) mice, and increased threefold with MRS2500 compared to vehicle. Tail BT was markedly prolonged in P2Y1(-/-) mice (7.9X) and in C57BL/6 mice given MRS2500. The current study demonstrates that P2Y1 deletion or antagonism significantly reduced venous thrombosis in mice, suggesting that P2Y1 receptors play a role in the pathogenesis of venous thrombosis, at least in this species. However as with many antithrombotic agents the benefit comes at the potential price of an increase in provoked bleeding times.     

Anemia as a factor related to the progression of proliferative diabetic retinopathy after photocoagulation

ObjectiveThis study aimed to investigate factors that could be related to the progression of proliferative diabetic retinopathy in patients treated with photocoagulation.MethodsIn this case-control study, a total of 106 patients with diabetic retinopathy participated who were treated with photocoagulation. We analyzed glycaemia, serum cholesterol, triglycerides, hemoglobin, platelet levels, blood pressure measurement, diabetes duration, diabetes and hypertension treatment, sex, and age. The statistical analysis was done with t test, χ² test, odds ratio (OR), and simple linear regression.ResultsWe found statistical significance in blood glucose level (P=.038), cholesterol level (P<.001), and hemoglobin level (P<.001). The simple linear regression was significant with blood glucose level (P<.05) and hemoglobin level (P=.001). Hemoglobin had a significant result: OR=2.432, 95% CI 1.902–3.115; Pearson χ²= 16.812; P<.001.ConclusionsAnemia is an important finding in diabetic patients. Anemia is a relevant factor related to the progression of proliferative diabetic retinopathy, which can be treated with photocoagulation.     

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation.MethodsA pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4 ± 5.98; duration of diabetes 12.4 ± 12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies.ResultsSignificant reductions in pain (? 18.1 ± 35.5 mm on a 100 mm scale, P = .05), neuropathic symptoms (? 1.24 ± 1.8 on MNSI, P = .01), and increased intraepidermal nerve fiber branching (+ 0.11 ± 0.15 branch nodes/fiber, P = .008) from a proximal skin biopsy were noted following the intervention.ConclusionsThis is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies.