Apart from its role in axon guidance, netrin-1 is also known to be
pro-angiogenic. The aim of this study is to determine whether adeno-associated
viral (AAV) mediated overexpression of netrin-1 improves post-stroke
neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of
1×1010 genome copies each was injected medial and
posterior to ischemic lesion at one hour following reperfusion using the distal
middle cerebral artery occlusion (MCAO) method. Quantitative RT-PCR revealed
that the expression of netrin-1 transgene began as early as one day and
increased dramatically about 3 weeks following vector injection. Western blot
analysis and confocal microscopy suggested that both the endogenous and
transduced netrin-1 were expressed in the neurons of the peri-infarct cortex
after MCAO. AAV-mediated netrin-1 overexpression significantly increased
vascular density in the peri-infarct cortex and promoted the migration of
immature neurons into the peri-infarct white matter, but it did not
significantly reduce infarct size. Netrin-1 overexpression also enhanced
post-stroke locomotor activity, improved exploratory behavior, and reduced
ischemia-induced motor asymmetry in forelimb usage. However, it had little
effect on post-stroke spatial learning and memory. Our results suggest that AAV
mediated netrin-1 overexpression improves peri-infarct vascular density and post
stroke motor function.
This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.
BackgroundInterventions providing foods fortified with multiple micronutrients can be a cost-effective and sustainable strategy to improve micronutrient status and physical growth of school children. We evaluated the effect of micronutrient-fortified yoghurt on the biochemical status of important micronutrients (iron, zinc, iodine, vitamin A) as well as growth indicators among school children in Bogra district of Bangladesh.MethodsIn a double-masked randomized controlled trial (RCT) conducted in 4 primary schools, 1010 children from classes 1–4 (age 6–9 years) were randomly allocated to receive either micronutrient fortified yoghurt (FY, n = 501) or non-fortified yoghurt (NFY, n = 509). For one year, children were fed with 60 g yoghurt everyday providing 30% RDA for iron, zinc, iodine and vitamin A. Anthropometric measurements and blood/urine samples were collected at base-, mid- and end-line. All children (FY, n = 278, NFY, n = 293) consenting for the end-line blood sample were included in the present analyses.ResultsBoth groups were comparable at baseline for socio-economic status variables, micronutrient status markers and anthropometry measures. Compliance was similar in both the groups. At baseline 53.4% of the population was anemic; 2.1% was iron deficient (ferritin <15.0 μg/L and TfR > 8.3 mg/L). Children in the FY group showed improvement in Hb (mean difference: 1.5; 95% CI: 0.4-2.5; p = 0.006) as compared to NFY group. Retinol binding protein (mean diff: 0.05; 95% CI: 0.002-0.09; p = 0.04) and iodine levels (mean difference: 39.87; 95% CI: 20.39-59.35; p < 0.001) decreased between base and end-line but the decrease was significantly less in the FY group. Compared to NFY, the FY group had better height gain velocity (mean diff: 0.32; 95% CI: 0.05-0.60; p = 0.02) and height-for-age z-scores (mean diff: 0.18; 95% CI: 0.02-0.33; p = 0.03). There was no difference in weight gain velocity, weight-for-age z-scores or Body Mass Index z-scores.ConclusionIn the absence of iron deficiency at baseline the impact on iron status would not be expected to be observed and hence cannot be evaluated. Improved Hb concentrations in the absence of a change in iron status suggest improved utilization of iron possibly due to vitamin A and zinc availability. Fortification improved height gain without affecting weight gain.Trial registrationClinicalTrial.gov: NCT00980733
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