Angiogenesis and neurogenesis are crucial processes for brain tissue repair and remodeling after brain injury. Current study shows that microRNA-210 (miR-210) promotes vascular endothelial cell migration and tube formation under hypoxia in vitro. Whether miR-210 overexpression promotes focal angiogenesis and neurogenesis in the normal adult brain is unknown. Adult male C57BL/6 mice (n=54) underwent stereotactic injection of a lentiviral vector carrying miR-210 (LV-miR-210). Following 28 days of miR-210 gene transfer, endothelial cell and neural precursor cell proliferation, microvessel density and downstream angiogenic factor were genotyped. miR-210 was highly expressed in neurons, astrocytes and endothelial cells of the LV-miR-210-injected brain hemisphere. The endothelial cell proliferation and the number of newly formed microvessels were greatly increased in the LV-miR-210-treated mice compared with the controls (P<0.05). Neural progenitor cells in the subventricular zone were greatly increased compared with the controls (P<0.05). The data indicate that miR-210 is a key factor at the microRNA level in promoting angiogenesis and neurogenesis, which was associated with local increased vascular endothelial growth factor (VEGF) levels, suggesting that miR-210 may be a potential target for ischemic stroke therapy.

No abstract

Knots form when polymers self-entangle, a process enhanced by compaction with important implications in biological and artificial systems involving chain confinement. In particular, new experimental tools are needed to assess the impact of multiple variables influencing knotting probability. Here, we introduce a nanofluidic knot factory for efficient knot formation and detection. Knots are produced during hydrodynamic compression of single DNA molecules against barriers in a nanochannel; subsequent extension of the chain enables direct assessment of the number of independently evolving knots. Knotting probability increases with chain compression as well as with waiting time in the compressed state. Using a free energy derived from scaling arguments, we develop a knot-formation model that can quantify the effect of interactions and the breakdown of Poisson statistics at high compression. Our model suggests that highly compressed knotted states are stabilized by a decreased free energy as knotted contour contributes a lower self-exclusion derived free energy.

MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P o 0.05). MiR-29b level negatively associated with NIHSS scores (r = − 0.349, P o0.01) and brain infarct volume (r = − 0.321, P o0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r = 0.723, P o 0.05). MiR-29b overexpression reduced infarct volume (49.50 ± 6.55 versus 35.48 ± 2.28 mm 3 , P o0.05), edema (164 ± 4% versus 108 ± 4%, Po 0.05), and blood-brain barrier (BBB) disruption compared with controls (15 ± 9% versus 7 ± 3%, P o 0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28 ± 7% versus 11 ± 3%, P o 0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P o0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4. (2015) 35, 1977-1984; doi:10.1038/jcbfm.2015.156; published online 1 July 2015 Journal of Cerebral Blood Flow & MetabolismKeywords: aquaporin-4; human; ischemia; microRNA-29b; stroke INTRODUCTION Acute ischemic stroke often results in the breakdown of bloodbrain barrier (BBB) and leads to vasogenic edema.1 Aquaporin-4 (AQP4) is an important water-channel protein in the central nervous system (CNS).2 It is particularly expressed at the perivascular foot processes of astrocytes, glia membranes, and ependymal cells. 3,4 Cerebral ischemia upregulates AQP4 expression, increases BBB permeability, and induces brain edema, which exacerbates ischemic brain injury. The level of AQP4 messenger RNA (mRNA) increases and peaks on day 3 after middle cerebral artery occlusion (MCAO) in rats.5 Aquaporin-4 knockout in mice protects neurocytes against cytotoxic edema caused by water intoxication and permanent focal cerebral ischemia. 6 It was reported recently that mesenchymal stem cells maintained BBB integrity by inhibiting AQP4 upregulation after cerebral ischemia.