کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6261826 | 1613257 | 2013 | 7 صفحه PDF | دانلود رایگان |

- Isoflurane preconditioning induces an acute phase of neuroprotection in mice.
- Isoflurane preconditioning-induced acute phase of neuroprotection may be mediated by Akt.
- Isoflurane preconditioning-induced acute phase of neuroprotection may depend on glutamate transporter type 3.
A pre-exposure to isoflurane reduces ischemic brain injury in rodents (isoflurane preconditioning). This neuroprotection has acute and delayed phases. Our previous in vitro studies suggest that the acute phase may involve excitatory amino acid transporters (EAATs). We determine whether this protection involves EAAT3, the major neuronal EAAT. Adult male EAAT3 knockout mice and their wild-type littermates were exposed or were not exposed to 1.5% isoflurane for 30Â min. Sixty minutes later, they were subjected to a 90- or 60-min middle cerebral arterial occlusion (MCAO). Their neurological outcomes were evaluated 24Â h after the MCAO. In another experiment, cerebral cortex was harvested for Western blotting at 30Â min after animals were exposed to 1.5% isoflurane for 30Â min. Here, we showed that isoflurane reduced brain infarct volumes and improved neurological functions of wild-type mice after a 90-min MCAO. However, isoflurane pre-exposure did not change the neurological outcome of EAAT3 knockout mice no matter whether the MCAO was for 90Â min or 60Â min. Isoflurane increased phospho-Akt, a survival-promoting protein, in the wild-type mice but not in the EAAT3 knockout mice. The isoflurane-induced neuroprotection in the wild-type mice was abolished by LY294004, an Akt activation inhibitor. LY294004 alone did not affect the neurological outcome of the wild-type or EAAT3 knockout mice after focal brain ischemia. These results suggest that the isoflurane preconditioning-induced acute phase of neuroprotection involves EAAT3. The downstream event includes Akt activation.
Journal: Brain Research Bulletin - Volume 98, September 2013, Pages 23-29