Spontaneously Hypertensive Rats Are Highly Vulnerable to AMPA-Induced Brain Lesions

Abstract

Background and Purpose-Whereas the effects of chronic arterial hypertension on the cerebral vasculature have been widely studied, its effects on brain tissue have been studied less so. Here we examined if spontaneously hypertensive rats (SHRs) or the normotensive control Wistar Kyoto rats (WKYs) made hypertensive by renal artery stenosis (R-WKYs) are vulnerable to an excitotoxic brain lesion provoked by an overactivation of glutamate receptors. Methods-Lesion volumes were quantified by histology in WKYs and SHRs subjected to striatal administration of

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

“…Nonetheless, data exist in the literature, although to a lesser extent, relative to SHR-SP, to show that hypertension per se does not entirely underlie the sensitivity of SHR to cerebral ischemia (Lecrux et al, 2007). Indeed, we have previously shown that 7-week-old SHR, in which hypertension is not yet established, also exhibit exacerbated ischemic brain damage when compared with agematched WKY (Lecrux et al, 2007). On the basis of these observations, we have used another wellcharacterized model of nongenetic hypertension, induced by renal artery stenosis in WKY (Del Bigio et al, 1999).…”

“…Indeed, eutrophic and hypertrophic remodeling of the brain arteries and the shift of the autoregulation curve are well-known hallmarks of the vascular changes induced in SHR (Mulvany et al, 1978). Nonetheless, data exist in the literature, although to a lesser extent, relative to SHR-SP, to show that hypertension per se does not entirely underlie the sensitivity of SHR to cerebral ischemia (Lecrux et al, 2007). Indeed, we have previously shown that 7-week-old SHR, in which hypertension is not yet established, also exhibit exacerbated ischemic brain damage when compared with agematched WKY (Lecrux et al, 2007).…”

“…Permanent focal cerebral ischemia was induced using the intraluminal approach (Lecrux et al, 2007). The rat was placed into a stereotaxic frame (Kopf Instruments, Tujunga, CA, USA) and a laser-Doppler flowmetry probe (FloLab Moor Instruments, Millwey, UK) was positioned on the right parietal bone, corresponding to the middle cerebral artery territory (coordinates 1.5 mm posterior, 5.5 mm lateral to the bregma), previously thinned by a salinecooled dental drill.…”

Lack of Neuroprotection of Inhibitory Peptides Targeting Jun/JNK after Transient Focal Cerebral Ischemia in Spontaneously Hypertensive Rats

“…Usually, overactivation of N-methyl-D-aspartic acid (NMDA) receptors leads to an increase in intracellular calcium levels and/or detrimental signaling pathways, which in turn can directly or indirectly cause much of the downstream damaging processes associated with ischemic stroke. In contrast, the SH rat has been shown to be much more sensitive than other strains to a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation (which has different downstream effects to NMDA) and to be relatively resistant to NMDA activation (Lecrux et al, 2007). To this end, JNKI-1D-TAT has shown high efficacy after NMDA excitotoxicity (Borsello et al, 2003) and we have also shown efficacy of PYC36D-TAT (and JNKI-1D-TAT) after NDMA exposure (unpublished observation).…”

Excitotoxic Stimulation of Brain Microslices as an <em>In vitro</em> Model of Stroke

“…The main advantages of these models are that they are easy to manipulate, relatively cost-effective, and cell death can be readily measured and quantitated. However, signaling pathways can be altered by the culturing conditions used 3,4 , and immature neurons and immortalized lines can express different receptors and signaling molecules when compared to mature brain [5][6][7][8] . Furthermore, cultured neurons only allow the examination of one cell type (or two, if a coculture system is used), whereas intact brain tissue is heterogeneous, containing a variety of cell types that interact with each other.…”