Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the ...

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1988.86

The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age.

Background and Purpose— The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of α-tocotrienol (TCT), but not α-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase. Methods— The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT. Results— Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to i...

http://tocomax.com.br/site/artigos/13.pdf

Neuroprotective Properties of the Natural Vitamin E α-Tocotrienol

The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2 = 40-45 mm Hg, PCO2 = 40-45 mm Hg, pH = 7.35-7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)-order arterioles were significantly (p less than 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p less than 0.05) larger in SHR compared to WKY. Only 1A and 4A has significantly (p less than 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10(-4) M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p greater than 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70-150 mm Hg and 100-200 mm Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p less than 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by vessel wall hypertrophy of the largest and smallest arterioles, was the major contributor to an upward shift in the autoregulatory range, the protection of exchange vasculature pressures, and the increase in vascular resistance.

Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats.

The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1990.61

Autoregulation of cerebral blood flow in experimental focal brain ischemia.

Genetic hypertension and increased susceptibility to cerebral ischemia.

Cerebral autoregulation was examined in NTR and SHR. The lower blood pressure limit of autoregulation being 95 mm Hg in SHR was shifted upwards from 62 mm Hg in NTR.

Lower limit of cerebral autoregulation in normotensive and spontaneously hypertensive rats

In SHR, CBP fell markedly and remained below 50 mm Hg after carotid occlusion despite SBP being elevated, while in NTR changes in CBP were related with changes in SBP. Vascular resistance of the brain in hypertensive rats is discussed.

M. Fujishima

Papers

Lower limit of cerebral autoregulation in normotensive and spontaneously hypertensive rats

Carotid back pressure following bilateral carotid occlusion in normotensive and spontaneously hypertensive rats.