We have previously shown that exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia-reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45-positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients.
( 1 − x ) Bi ( Zn 1 / 2 Ti 1 / 2 ) O 3 − x BaTiO 3 polycrystalline ceramics were obtained via solid state processing techniques. The perovskite structure was found to be stable for compositions containing x=0.66 or greater. Based on x-ray diffraction data, a morphotropic phase boundary between tetragonal and rhombohedral perovskite phases was observed at x≈0.9. For compositions rich in BaTiO3, the symmetry of the perovskite phase was tetragonal but with increased Bi(Zn1/2Ti1/2)O3 content, the rhombohedral phase appeared. Dielectric characterization revealed that as Bi(Zn1/2Ti1/2)O3 content increased, the transition temperature decreased and the transition peak became very diffused. A comparison of the dielectric behavior with other Bi(Zn1/2Ti1/2)O3-based solid solutions is also discussed.
In this paper, the development of a novel low power (mW), low current (mA) AC microfluidic pump is described that is capable of generating kPa head pressures. AbstractThis paper details the development of an integrated AC electro-osmotic (ACEO) microfluidic pump for dilute electrolytes consisting of a long serpentine microchannel lined with three dimensional (3D) stepped electrode arrays. Using low AC voltage (1 Volt rms, 1 kHz), power (5 mW) and current (3.5 mA) in water, the pump is capable of generating a 1.4 kPa head pressure, a 100-fold increase over prior ACEO pumps, and a 1.37 mm/sec effective slip velocity over the electrodes without flow reversal. The integrated ACEO pump can utilize low ionic strength solutions such as distilled water as the working solution to pump physiological strength (100 mM) biological solutions in separate microfluidic devices, with potential applications in portable or implantable biomedical microfluidic devices. As a proof-of-concept experiment, the use of the ACEO pumps for DNA hybridization in a microfluidic microarray is demonstrated.
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