Clotilde Lecrux et al.,
University of Caen, France.
Stroke. 2007
http://stroke.ahajournals.org/content/38/11/3007.full.pdf+html
The fact that chronic arterial hypertension is a major risk factor for cerebral ischemia is well known. However the mechanisms by which arterial hypertension induces brain damage is unknown. In this study the authors were interested in two important steps that could possibly result in understanding the mechanisms. First they compared the evolution of cerebral blood flow during transient ischemia, using a Doppler flowmetry probe between SHRs and WKYs. Secondly they examined the amount of brain damage induced by the administration of NMDA or AMPA (because following ischemia there is overactivation of these ionotropic glutamate receptors) into the striatum using 20 um section stained by thionin. Thirdly since in the SHRs the hypertension develops over a period of time as a control, hypertension was induced in a group of 5 weeks old WKYs rats by renal arterial stenosis and tested over a period of time. Finally they tested whether the increased sensitivity of SHRs to AMPA receptors is linked to the differential expression of its subunits in the striatum using western blot and RT-PCR. The present study provides evidence that SHRs show more specificity to AMPA receptors activation. Even though the levels of AMPA receptors subunits GluR1 and GluR2 were similar between both the strains, the phosphorylated form, pGluR1 is significantly higher in SHRs compared to WKYs. Further SHRs also expressed higher levels of CamKIIalpha protein in the striatum compared to WKYs. In addition, inhibition of this kinase significantly reduced the deleterious effects of AMPA receptors overactivation in the SHRs. This article suggests that phosphorylation of AMPA receptors, at least in part may explain the propensity of this strain (SHRs) to stroke.
- Madhan
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