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Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice
Hamdard College of Medicine and Dentistry, Hamdard University, Sharae Madinat Al-Hikmah, Karachi 74600, Pakistan
Center for Neuroscience, Aging and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
* Author to whom correspondence should be addressed.
Received: 5 May 2013; in revised form: 18 June 2013 / Accepted: 27 June 2013 / Published: 22 July 2013
Abstract: Transient global cerebral ischemia causes delayed neuronal death in the hippocampal CA1 region. It also induces an up regulation of cyclooxygenase 2 (COX-2), which generates several metabolites of arachidonic acid, known as prostanoids, including Prostaglandin I2 (PGI2). The present study investigated whether the PGI2 IP receptor plays an important role in brain injury after global cerebral ischemia in aged mice. Adult young (2–3 months) and aged (12–15 months) male C57Bl/6 wild-type (WT) or IP receptor knockout (IP KO) mice underwent a 12 min bilateral common carotid artery occlusion (BCCAO) or a sham surgery. Behavior tests (neurologic deficit and T-maze) were performed 3 and 7 days after BCCAO. After seven days of reperfusion, the numbers of cells positive for markers of neurons, astrocytes, microglia, myeloperoxidase (MPO) and phosphorylated CREB (p-CREB) were evaluated immunohistochemically. Interestingly, in young and aged IP KO ischemic mice, there was a significant increase (p < 0.01) in cognitive deficit, hippocampal CA1 pyramidal neuron death, microglia and MPO activation, while p-CREB was reduced as compared to their corresponding WT controls. These data suggest that following ischemia, IP receptor deletion contributes to memory and cognitive deficits regulated by the CREB pathway and that treatment with IP receptor agonists could be a useful target to prevent harmful consequences.
Keywords: global cerebral ischemia; aging; cognitive deficit; prostaglandin I2; mouse
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MDPI and ACS Style
Shakil, H.; Saleem, S. Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice. Brain Sci. 2013, 3, 1095-1108.
Shakil H, Saleem S. Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice. Brain Sciences. 2013; 3(3):1095-1108.
Shakil, Hania; Saleem, Sofiyan. 2013. "Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice." Brain Sci. 3, no. 3: 1095-1108.