Systems neuroscienceProstacyclin receptor deletion aggravates hippocampal neuronal loss after bilateral common carotid artery occlusion in mouse
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Animals
Experiments and procedures were conducted in accordance with the National Institutes of Health guidelines for the use of experimental animals. Protocols were approved by the Johns Hopkins Animal Care and Use Committee and were designed to minimize distress and number of animals. WT and IP−/− C57Bl/6 male mice (22–29 g) were obtained from our breeding colony, which was originated by Dr. Shuh Narumiya (Kyoto University, Kyoto, Japan) (Murata et al., 1997), and genotyped as described previously (
Mouse genotype and cerebral vessel anatomy
Polymerase chain reaction confirmed the IP−/− genotype of the mice (Fig. 1A). Because vessel anatomy/plasticity of the PcomA can affect outcome in the global ischemia model, we compared the major features of vessel anatomy of the mice. We found that the vessel anatomy of the PcomA of the IP−/− and WT mice was not remarkably different. Following the scale system of Murakami et al. (1997), the mean score values of PcomA plasticity were 1.5±0.2 in IP−/− (n=12) and 1.3±0.2 in WT (n=10) mice. The
Discussion
In this study, we showed that in mice subjected to 12 min of forebrain global cerebral ischemia followed by 7 days of reperfusion, genetic deletion of the PGI2 IP receptor results in greater delayed neuronal loss in the CA1 region of the hippocampus than that seen in WT mice. The data imply a protective role for the IP receptor in delayed pyramidal neuron cell death. Our findings in C57Bl/6 male mice are also consistent with those of other studies showing that relatively selective IP receptor
Acknowledgments
The authors would like to thank Claire Levine for her assistance in preparing this manuscript and Adam Sapirstein, Zengjing Yang, Ité Alonzo, Ellen Gordes, and every member of the Doré laboratory team for their helpful contributions. Part of this work was presented at the 2006 annual meeting of the Society for Neuroscience, Atlanta, GA. Grant support: This work was supported in part by the National Institutes of Heath: NINDS (NS046400) and the NIA (AG022971) (S.D.).
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2011, Free Radical Biology and MedicineCitation Excerpt :Our previous study demonstrated that interrupted reperfusion has neuroprotective effects in global cerebral ischemic injury in rats [28], and the present study extended this finding to mice [29]. C57BL/6 mice have a poorly developed Circle of Willis, and bilateral common carotid arterial occlusion is widely used to establish global cerebral ischemia in this strain [30–34]. In the preliminary study, we used a Doppler blood-flow meter (ML 191; AD Instruments) and needle probe (MNP 110XP; AD Instruments) to measure the regional cerebral blood flow (rCBF) at 3.5 mm right or left (randomly) of the bregma [35] and found the rCBFs were reduced more than 90% of baseline.
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2010, NeuroscienceCitation Excerpt :The LDF signal, body temperature, and MABP also did not differ between the two groups (Fig. 1). We have previously reported that there are no obvious differences in gross cerebrovascular anatomy between the WT and the IP−/− groups (Wei et al., 2008). In addition, no significant differences in physiological parameters were observed between mice administered the effective dose of beraprost (100 μg/kg) and those administered vehicle [MABP (90–80 mm Hg), temperature (37.0–37.5 °C), and pH (7.34–7.37)].
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