Gene transfection with Notch 1 intracellular domain and subsequent growth factor treatment stimulate neuron-like differentiation of bone marrow stromal cells (BMSCs). Here, we examined the potential of transplanting Notch-induced BMSCs to exert therapeutic effects in a rat model of chronic ischemic stroke. In experiment 1, Notch-induced rat BMSCs were intrastriatally transplanted in rats at 1 month after being subjected to transient occlusion of middle cerebral artery (MCAo). Compared to post-stroke/pretransplantation level, significant improvements in locomotor and neurological function were detected in stroke rats that received 100 k and 200 k BMSCs, but not in those that received 40 k BMSCs. Histological results revealed 9%-15% graft survival, which dose-dependently correlated with behavioral recovery. At 5 weeks post-transplantation, some grafted BMSCs were positive for the glial marker GFAP (about 5%), but only a few cells (2-5 cells per brain) were positive for the neuronal marker NeuN. However, at 12 weeks post-transplantation, where the number of GFAP-positive BMSCs was maintained (5%), there was a dramatic increase in NeuN-positive BMSCs (23%). In experiment 2, Notch-induced human BMSCs were intrastriatally transplanted in rats at 1 month following the same MCAo model. Improvements in both locomotor and neurological function were observed from day 7 to day 28 post-transplantation, with the high dose (180 k) displaying significantly better behavioral recovery than the low dose (90 k) or vehicle. There were no observable adverse behavioral effects during this study period that also involved chronic immunosuppression of all animals. Histological analyses revealed a modest 5%-7% graft survival, with few (<1%) cells expressing an intermediate MAP2 neuronal marker, but not glial or oligodendroglial markers. In addition, striatal peri-infarct cell loss was significantly reduced in transplanted stroke animals compared to vehicle-treated stroke animals. The present study demonstrates the potential of Notch-induced BMSC cell therapy for patients presenting with fixed ischemic stroke.
Most metal–organic‐framework‐ (MOF‐) based hybrid membranes face the challenge of low gas permeability in CO2 separation. This study presents a new strategy of interweaving UiO‐66 and PIM‐1 to build freeways in UiO‐66‐CN@sPIM‐1 membranes for fast CO2 transport. In this strategy, sPIM‐1 is rigidified via thermal treatment to make polymer voids permanent, and concurrently polymer chains are mutually linked onto UiO‐66‐CN crystals to minimize interfacial defects. The pore chemistry of UiO‐66‐CN is kept intact in hybrid membranes, allowing full utilization of MOF pores and selective adsorption for CO2. Separation results show that UiO‐66‐CN@sPIM‐1 membranes possess exceptionally high CO2 permeability (15433.4–22665 Barrer), approaching to that of UiO‐66‐NH2 crystal (65–75% of crystal‐derived permeability). Additionally, the CO2/N2 permeation selectivity for a representative membrane (23.9–28.6) moves toward that of single crystal (24.6–29.6). The unique structure and superior CO2/N2 separation performance make UiO‐66‐CN@sPIM‐1 membranes promising in practical CO2 separations.
Background: Minocycline, a second-generation tetracycline with anti-inflammatory and antiapoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.
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