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Suggesting a mechanism involving modulation of the inflammatory response, sildenafil significantly decreased microglial density at 72 h and 8 days after pMCAo. Nevertheless, it provided a significant dose-dependent reduction of mean lesion extent 8 days after pMCAo.
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ResultsĪlthough sildenafil (10 mg/kg) treatment potently increased cGMP concentrations, it did not influence early collateral recruitment nor did it reduce mean infarct volumes 72 h after pMCAo. Expression of M1- and M2-like microglia/macrophage markers were analyzed. Animals were euthanized, and brain tissues were obtained at 72 h or 8 days after pMCAo.
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Blood flow (BF) velocities were measured by ultrasound imaging with sequential Doppler recordings and laser speckle contrast imaging. Ischemia was induced in C57Bl/6 mice on postnatal (P) day 9 by permanent middle cerebral artery occlusion (pMCAo), and followed by either PBS or sildenafil intraperitoneal (i.p.) injections. The present study investigated the effects of sildenafil in a neonatal mouse stroke model on (1) hemodynamic changes and (2) regulation of astrocyte/microglia-mediated neuroinflammation. We have previously demonstrated a beneficial effect of sildenafil citrate, a PDE-5 inhibitor, on stroke lesion size in neonatal rat pups. Perinatal ischemic stroke is the most frequent form of cerebral infarction in neonates however, evidence-based treatments are currently lacking.