| First Author | Wang Y | Year | 2008 |
| Journal | Eur J Neurosci | Volume | 28 |
| Issue | 1 | Pages | 51-61 |
| PubMed ID | 18662334 | Mgi Jnum | J:139957 |
| Mgi Id | MGI:3810862 | Doi | 10.1111/j.1460-9568.2008.06304.x |
| Citation | Wang Y, et al. (2008) Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia. Eur J Neurosci 28(1):51-61 |
| abstractText | We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)-mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min of middle cerebral artery occlusion were similar in wild-type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/-) mice. NHE1+/+ mice developed infarct volume of 57.3 +/- 8.8 mm(3) at 24 h reperfusion (Rp), which progressed to 86.1 +/- 10.0 mm(3) at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis-inducing factor (AIF), activation of caspase-3, and TUNEL-positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/- mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase-3 was significantly reduced in NHE1+/- brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up-regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis. |
