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  • 1
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Ionic channels appear to play an important role in contractile responses of the cerebral arteries and, thereby, contribute to the regulation of cerebral circulation. In the present study, we investigated the role of large-conductance Ca2+-activated K+ (BKCa) channels in the regulation of cerebral arterial tone during chronic hypertension.2. Ring segments of the basilar artery from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were placed in bath chambers and the isometric tension of each ring was measured.3. Application of inhibitors of BKCa channels, namely tetraethylammonium (TEA; ≥ 0.1 mmol/L) and charybdotoxin (CTX; ≥ 0.1 nmol/L), produced spontaneous contraction with rhythmic oscillation in the basilar artery from SHR.4. The oscillatory contraction was not induced by 5-hydroxytryptamine (0.01–10 μmol/L) or depolarization by external high K+ (20–60 mmol/L).5. The rhythmic contraction was completely abolished by either the removal of external Ca2+ or the application of nicardipine (10 nmol/L).6. The oscillation was not affected by the substitution of external Cl– by various equimolar anions (i.e. acetate, benezenesulphonate, bromide and isethianate).7. The amplitude of the oscillation was dose-dependently increased by the vasodilators forskolin and sodium nitroprusside, as well as by stimulation of the endothelium with histamine and acetylcholine, whereas the frequency was decreased.8. In contrast, the oscillation was eliminated by depletion of Ca2+ stores by caffeine. Neither TEA (10 mmol/L) nor CTX (10 nmol/L) produced any significant contraction of the basilar artery in WKY rats.9. These results suggest that BKCa channels may play an important role in regulating the resting tone of the cerebral artery in SHR.
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  • 2
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in ...
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  • 3
    ISSN: 1573-6903
    Keywords: Hippocampus ; striatum ; spontaneously hypertensive rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Heat shock proteins (HSPs) induced by brain ischemia may play an important role in neuroprotection from neuronal degeneration. In this study, we examined the cerebral blood flow (CBF) threshold to produce regional differences in HSP72 induction after transient forebrain ischemia in spontaneously hypertensive rats (SHRs). Female SHRs were subjected to 20 min of cerebral ischemia induced by bilateral carotid artery occlusion. The CBF was measured by laser Doppler flowmetry. At forty-eight hours after cerebral ischemia and reperfusion, the rats were decapitated and the brains were removed. Specific areas (hippocampal CA1, CA2-3, dentate gyrus, dorsolateral and ventromedial striatum, and parietal cortex) were thereafter dissected from the brain. The amounts of HSP72 in these samples were determined using Western blot analysis. In the hippocampus, HSP72 was induced when the CBF decreased to less than 18–25% of the resting level. The mean values of HSP72 produced in the CA1 area, CA2-3 area, and the dentate gyrus following ischemia and reperfusion treatment were 4.44 ± 1.43 (±SD) ng/μg prtein, 3.51 ± 0.72 ng/μg protein and 3.77 ± 1.05 ng/μg protein, respectively. In the parietal cortex, the amount of HSP72 induction was less pronounced (2.55 ± 0.40 ng/μg protein), while HSP72 was hardly detected at all in the striatum, even under conditions of very severe CBF reduction and reperfusion. We demonstrated the existence of both a CBF threshold (i.e., approximately 20% of the resting level) for HSP72 induction and regional heterogeneity for the induction of HSP72 protein.
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  • 4
    ISSN: 1573-6903
    Keywords: Hypothermia ; cerebral ischemia ; cerebral blood flow ; brain tissue metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the effect of selective hypothermia of the brain (brain cooling) on regional cerebral blood flow and tissue metabolism, we have developed a brain thermo-regulator. Brain temperature was modulated by a water-cooled metallic plate placed on the surface of the rats' scalp to get the appropriate brain temperature precisely with ease. Regional cerebral blood flow and brain temperature were measured simultaneously using a Teflon-coated platinum electrode and thermocouple probe inserted stereotaxically into the parietal cortex and thalamus in spontaneously hypertensive rats. Experimental forebrain ischemia was induced by the occlusion of bilateral common carotid artery under normo- and hypothermic brain condition, and the supratentorial brain tissue metabolites were measured enzymatically after 60 min of forebrain ischemia. When cortical temperature was set to hypothermia, cortical blood flow was significantly lowered by 40% at 30°C and 20% at 33°C as compared with that at 36°C (p 〈 0.0001 and p 〈 0.05, respectively). Thalamic blood flow was also significantly reduced by 20% when cortical temperature was set to 30°C as compared with 36°C (p 〈 0.05). There were no significant differences in arterial blood pressure and gas parameters throughout these experiments. In the rats with selective brain hypothermia (30°C) immediately after the induction of cerebral ischemia, the level of brain ATP concentration after 60 min of ischemia was significantly higher than that in normothermia rats (36°C) (p 〈 0.05). Our findings indicate that: 1) the metallic plate brain thermo-regulator is useful in small animal experiments; 2) regional brain temperature regulates regional cerebral blood flow; and 3) selective brain hypothermia, even started after the forebrain ischemia, ameliorates the derangement of brain metabolism, suggesting its effectiveness as a cytoprotective strategy.
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  • 5
    ISSN: 1573-6903
    Keywords: Aging ; DNA ; RNA ; brain ; SHR ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the effects of aging accompanied with hypertension on brain nucleic acid, we measured both the DNA and RNA contents of six specific brain regions in adult (5–6 months old) and aged (18–22 months old) female spontaneously hypertensive rats (SHRs). Although no statistical difference was observed in the RNA content, the DNA content did tend to increase in the hippocampal CA1 of aged SHR (4.24 ± 0.55 ng/μg protein, mean ± SD, n = 6) in comparison to that of adult SHR (3.21 ± 0.71 ng/μg protein, n = 4). Hence, aged SHRs showed a significant decrease in the RNA to DNA ratio in the CA1 subfield of the hippocampus (3.79 ± 0.61) compared to adult SHR (5.27 ± 0.81). On the other hand, no other regions, except for the dorsolateral region of the striatum, showed any difference in the RNA/DNA ratio between aged and adult SHR. We therefore conclude that subtle changes in the nucleic acid occur in vulnerable regions of the brain in aged SHRs.
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  • 6
    ISSN: 1573-6903
    Keywords: Cerebral ischemia ; dopamine release ; flow threshold ; in vivo brain dialysis ; striatum ; spontaneously hypertensive rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the level of cerebral blood flow reduction which causes striatal dopamine release, extracellular dopamine and cerebral blood flow was simultaneously determined using in vivo brain dialysis and a hydrogen clearance method, respectively, in the striatum of spontaneously hypertensive rats, before and during experimental cerebral ischemia. The ischemic flow threshold for neurotransmitter dopamine release was found to be 20% of the resting value or 8–10 ml/100g/min of cerebral blood flow, being similar to those for energy and membrane failures.
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  • 7
    ISSN: 1573-6903
    Keywords: Cerebral ischemia ; cerebral blood flow ; brain metabolism ; steal phenomenon ; aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral blood flow (CBF) and cerebellar blood flow (CeBF) were measured and correlated with brain lactate, pyruvate and adenosine triphosphate concentrations from groups representing 3-week old suckling (n = 10), 18–22-week old adult (n = 9) and 70-week old aged (n = 7) Sprague-Dawley rats before and during bilateral carotid occlusion (BCO). The steal ratio, calculated as the ratio of %control CBF to %control CeBF, was 1.02 ± 0.06 (mean ± SEM) at 60 minutes of BCO in adult rats that exhibited normal levels of brain metabolites. By contrast, the ratios significantly decreased to 0.74 ± 0.06 in suckling rats and 0.69 ± 0.06 in aged rats with simultaneous increases by 2.4 to 2.9-fold of tissue lactate. Pyruvate and lactate/pyruvate ratio also increased by 1.4 to 1.8 times control in both suckling and aged rats. We conclude that there is age-related steal phenomenon occurring with blood flow during BCO. Ischemic derangement of the brain metabolism is in part related to poor blood supply from the posterior circulation in suckling and aged rats.
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  • 8
    ISSN: 1573-6903
    Keywords: Calcium antagonist ; isradipine ; spontaneously hypertensive rats (SHR) ; incomplete cerebral ischemia ; brain tissue metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.
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  • 9
    ISSN: 1573-2568
    Keywords: brain ischemia ; gastric mucosal blood flow ; integrity of the gastric mucosa ; vagal adrenergic pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through α1-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.
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