Rosiglitazone ameliorates tissue plasminogen activator-induced brain hemorrhage after stroke.

OBJECTIVE: Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator-activated receptor-γ (PPAR-γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti-inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA-induced HT after stroke. METHODS AND RESULTS: We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10 mg/kg, 2 hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA-induced HT. When RSG(6 mg/kg) was intraperitoneally administered 1 hour before MCAO in tPA-treated MCAO mice, HT in the ischemic territory was significantly attenuated 1 day after stroke. In the tPA-treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA-alone-treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down-regulated in microglia of the RSG-treated mice. We further found that the expression of Arg-1 was also upregulated in those tPA and RSG-treated stroke mice and the protection against tPA-induced HT and BBB disruption in these mice were abolished in the presence of PPAR-γ antagonist GW9662 (4 mg/kg, 1 hour before dMCAO through intraperitoneal injection). CONCLUSIONS: RSG treatment protects against BBB damage and ameliorates HT in delayed tPA-treated stroke mice by activating PPAR-γ and favoring microglial polarization toward anti-inflammatory phenotype.

Ultra-Sensitive Strain Sensor Based on Flexible Poly(vinylidene fluoride) Piezoelectric Film.

A flexible 4 × 4 sensor array with 16 micro-scale capacitive units has been demonstrated based on flexible piezoelectric poly(vinylidene fluoride) (PVDF) film. The piezoelectricity and surface morphology of the PVDF were examined by optical imaging and piezoresponse force microscopy (PFM). The PFM shows phase contrast, indicating clear interface between the PVDF and electrode. The electro-mechanical properties show that the sensor exhibits excellent output response and an ultra-high signal-to-noise ratio. The output voltage and the applied pressure possess linear relationship with a slope of 12 mV/kPa. The hold-and-release output characteristics recover in less than 2.5 µs, demonstrating outstanding electro-mechanical response. Additionally, signal interference between the adjacent arrays has been investigated via theoretical simulation. The results show the interference reduces with decreasing pressure at a rate of 0.028 mV/kPa, highly scalable with electrode size and becoming insignificant for pressure level under 178 kPa.