Friday, September 6, 2013

Isoflurane post-conditioning protects primary cultures of cortical neurons against oxygen and glucose deprivation injury via upregulation of Slit2/Robo1

You do expect your doctor to use this knowledge for your next stroke? Or why the hell are you paying them any money? Did they do that good a job that you recovered 100% from your last stroke? Paying for results is the only way to go.
http://www.sciencedirect.com/science/article/pii/S0006899313011736
  • a Department of Anesthesiology, ShengJing Hospital, China Medical University, Shenyang, China
  • b Department of Neurology, The Ninth People's Hospital, Shanghai Jiaotong University, School of medicine, Shanghai, China
  • c Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • d Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China
  • e Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

Highlights

Clinical relevant concentration of Isoflurane has neuroprotective effect on neuron.
Isoflurane post-conditioning attenuates apoptosis of neurons after OGD/R injury.
This effect may be mediated by increases in the expression of Slit2 and Robo1.

Abstract

Different mechanisms have been suggested to contribute to isoflurane-mediated neuroprotection. Previous studies have suggested that the protein Slit can abrogate neuronal death in mixed neuronal–glial cultures exposed to oxygen–glucose deprivation (OGD) and reperfusion (OGD/R). We hypothesized that isoflurane increases the expression of Slit and its receptor Robo when cortical neurons are exposed to OGD/R. To test this hypothesis, we exposed primary cortical neurons to OGD for 90 min and reperfusion for 24 h and investigated how isoflurane post-conditioning affected cell survival and expression of Slit2 and receptors Robo1 and Robo4. Cell survival increased after administration of isoflurane, as assessed by the lactate dehydrogenase assay, trypan blue analysis, and propidium iodide staining. Western blot analysis showed that cleaved caspase-3 was increased after OGD/R(P<0.01) but reduced by isoflurane post-conditioning. Real-time PCR and Western blot analysis showed that the expression levels of Slit2 and Robo1, but not Robo4, were increased after OGD/R (P<0.5) and increased even further by isoflurane post-conditioning (P<0.01). Our results suggest that isoflurane post-conditioning markedly attenuates apoptosis and necrosis of cortical neurons exposed to OGD/R possibly in part via elevation of Slit2/Robo1 expression. These findings provide a novel explanation for the pleiotropic effects of isoflurane that could benefit the central nervous system.

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