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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.
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PMID:Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion. 170 54

This investigation involved alterations in the local control of vascular tone in the isolated rabbit basilar artery in atherosclerosis, with Watanabe heritable hyperlipidemic (WHHL) rabbits as a model and New Zealand White (NZW) rabbits as controls. Vasoconstrictor responses to KCl in isolated preparations of the basilar artery at basal tone showed no differences at 4, 6, and 12 months of age in either WHHL or NZW rabbits. Contractile responses to both histamine and neuropeptide Y were significantly greater in 12-month-old WHHL rabbit preparations when compared with responses measured at 4 and 6 months. In NZW rabbit preparations, there was no change in maximum contractile responses to both histamine and neuropeptide Y over the same age range. Endothelium-dependent relaxations to acetylcholine in raised-tone preparations from WHHL rabbits were significantly greater at 6 months in comparison with responses measured at both 4 and 12 months of age. In contrast, endothelium-independent relaxations to calcitonin gene-related peptide and vasoactive intestinal polypeptide showed no change over the age range studied. In NZW rabbit preparations, both endothelium-dependent and endothelium-independent relaxations declined significantly between 4 and 12 months. The significance of these changes in the rabbit basilar artery in atherosclerosis is discussed in relation to the "protection" of intracranial arteries from atherosclerosis and their subsequent susceptibility to cerebral ischemia and stroke.
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PMID:Changes in vasoconstrictor and vasodilator responses of the basilar artery during maturation in the Watanabe heritable hyperlipidemic rabbit differ from those in the New Zealand White rabbit. 191 1

An infusion of calcitonin-gene-related peptide (CGRP) at progressively increased concentrations was given to 15 patients with neurological deficits after intracranial aneurysm surgery for subarachnoid haemorrhage. In 9 of the patients the deficits, quantified by a modified Glasgow coma scale, improved with no adverse effects; after a placebo infusion only 2 of the 15 patients showed improvement. If CGRP can reverse cerebral ischaemia after early intracranial aneurysm surgery, its use may improve the safety of such early surgery, remove the need for late surgery with its increased risk of death from rebleeding, and reduce overall morbidity and mortality of aneurysmal subarachnoid haemorrhage.
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PMID:Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage. 196 82

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17% under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postischemic cerebral blood flow and neuroeffector mechanisms. 200 79

Cerebral ischemia induces transcriptional changes in a number of pathophysiologically important genes. Here we have systematically studied gene expression changes in the cortex after 150 min of focal cortical ischemia and 2 and 6 h reperfusion in the mouse by a fragment display technique (restriction-mediated differential display, RMDD). We identified 57 transcriptionally altered genes, of which 46 were known genes, and 11 unknown sequences. Of note, 14% of the regulated genes detected at 2 h reperfusion time were co-regulated in the contralateral cortex. Four genes were verified to be upregulated by quantitative PCR. These were Metallothionein-II (mt2), Receptor (calcitonin)-activity modifying protein 2 (ramp2), Mitochondrial phosphoprotein 65 (MIPP65), and the transcription elongation factor B2/elongin B (tceb). We could identify several genes that are known to be induced by cerebral ischemia, such as the metallothioneins and c-fos. Many of the genes identified provide hints to potential new mechanisms in ischemic pathophysiology. We discuss the identity of the regulated genes in view of their possible usefulness for pharmacological intervention in cerebral ischemia.
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PMID:Identification of regulated genes during transient cortical ischemia in mice by restriction-mediated differential display (RMDD). 1509 82

Adrenomedullin (AM) has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of delayed AM gene transfer in cerebral ischemia. Three days after a 1-hr occlusion of the middle cerebral artery (MCAO), rats were injected intravenously with adenovirus harboring human AM cDNA. The experiment was terminated 7 days after MCAO. AM gene transfer significantly reduced cerebral infarct size compared with that of rats before virus injection and compared with that of rats injected with control virus. The expression of recombinant human AM was identified in ischemic brain by immunostaining. Morphological analyses showed that AM gene transfer enhanced the survival and migration of astrocytes into the ischemic core. Cerebral ischemia markedly increased astrocyte apoptosis, and AM gene delivery significantly reduced apoptosis to near normal levels as seen in sham control rats. Similarly, in primary cultured astrocytes, AM stimulated cell migration and inhibited hypoxia/reoxygenation-induced apoptosis. The effects of AM on both migration and apoptosis were abolished by calcitonin gene-related peptide [CGRP(8-37)], an AM receptor antagonist. Enhanced cell survival after AM gene transfer was accompanied by markedly increased cerebral nitric oxide and Bcl-2 levels, as well as Akt and GSK-3beta phosphorylation, but reduced NADPH oxidase activity and superoxide production. Inactivation of GSK-3beta by phosphorylation led to reduced GSK-3beta activity and caspase- 3 activation. These results indicate that exogenous AM provides neuroprotection against cerebral ischemia injury by enhancing astrocyte survival and migration and inhibiting apoptosis through suppression of oxidative stress-mediated signaling events.
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PMID:Adrenomedullin gene delivery protects against cerebral ischemic injury by promoting astrocyte migration and survival. 1568

Adrenomedullin (AM) is a peptide hormone widely distributed in the central nervous system. Our previous study showed that AM gene delivery immediately after middle cerebral artery occlusion (MCAO) protected against cerebral ischemia/reperfusion (I/R) injury by promoting glial cell survival and migration. In the present study, we investigated the effect of delayed AM peptide infusion on ischemic brain injury at 24 h after MCAO. AM infusion significantly reduced neurological deficit scores at days 2, 4, and 8 after cerebral I/R. AM reduced cerebral infarct size at 8 and 15 days after surgery as determined by quantitative analysis. Double staining showed that AM infusion reduced TUNEL-positive apoptotic cells in both neurons and glial cells, as well as reduced caspase-3 activity in the ischemic area of the brain. In addition, AM treatment increased capillary density in the ischemic region at 15 days after I/R injury. Parallel studies revealed that AM treatment enhanced the proliferation of cultured endothelial cells as measured by both (3)H-thymidine incorporation and in situ BrdU labeling. Both in vitro and in vivo AM effects were blocked by calcitonin gene-related peptide (8-37), an AM receptor antagonist. Moreover, AM's effects were associated with increased cerebral nitric oxide (NO) levels, as well as decreased NAD(P)H oxidase activities and superoxide anion production. These results indicate that a continuous supply of exogenous AM peptide protects against I/R injury by improving the survival of neuronal and glial cells, and promoting angiogenesis through elevated NO formation and suppression of oxidative stress.
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PMID:Postischemic infusion of adrenomedullin protects against ischemic stroke by inhibiting apoptosis and promoting angiogenesis. 1634 85

Electroacupuncture (EA) is widely used to treat disorders of the nervous system, such as stroke. The aim of the present study was to investigate the effect of EA on cerebral blood flow (CBF) in cerebral ischemic rats. We developed an animal model of cerebral ischemia (CI) by occluding the blood flow of both common carotid arteries in Sprague-Dawley (SD) rats; 2 or 15 Hz EA was applied to both Zusanli acupoints. The levels of nitric oxide (NO) in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus were measured. In addition, L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF induced by EA in rats with and without CI. The results indicated that both 2 and 15 Hz EA increase the mean CBF in rats with and without CI. However, neither 2 nor 15 Hz EA induced changes in levels of NO in peripheral blood or changes in CGRP levels in cerebral cortex and thalamus. In addition, L-NAME did not change the increase in CBF. We concluded that both 2 and 15 Hz EA at both Zusanli acupoints induced the increase of CBF in rats with and without CI. Whether the effect of EA is related to NO or CGRP will be investigated in a future study.
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PMID:The study of electroacupuncture on cerebral blood flow in rats with and without cerebral ischemia. 1655 44

The present study has been designed to investigate the role of insulin, endogenous opioids and calcitonin gene related peptide (CGRP) on remote mesenteric ischaemic preconditioning induced reversal of global cerebral ischaemia-reperfusion injury in mice. Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hour was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking and resistance to lateral push response, tests were employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly, ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Anti-insulin serum, naloxone (an opioid receptor antagonist) and alpha-CGRP (8-37) (a selective CGRP receptor blocker) attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning probably is mediated through insulin, endogenous opioids and CGRP released as a consequence of mesenteric ischaemia and reperfusion in mice.
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PMID:Possible involvement of insulin, endogenous opioids and calcitonin gene-related peptide in remote ischaemic preconditioning of the brain. 1754 Dec 53

High is the incidence of gastrointestinal dysfunction induced by cerebrovascular disease. However, little is known about the effects of CGRP on gastrointestinal injuries induced by cerebrovascular disease. The purpose of the present study was to investigate the protective effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion in rats. Thirty healthy adult male Wistar rats were selected for this experiment and were randomly divided into CGRP-treated, sham-operated, and control groups, respectively. Ten rats were involved in each group. Focal cerebral ischemia reperfusion rat model was established by a 2-hour left middle cerebral artery occlusion (MCAO) using an intraluminal filament, followed by 46h of reperfusion. CGRP (1 microg/ml) at the dose of 3 microg/kg was injected intraperitoneally (i.p.) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3 ml/kg body weight), i.p., was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without MCAO. Forty-eight hours after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy, determining mast cell distribution by toluidine blue staining, and observing the expression of gastrin (Gas), somatostatin (SST), aquaporin-4 (AQP4), and basic fibroblast growth factor (bFGF) by immunohistochemical staining. The results showed that: (1) Gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, infiltration of inflammatory cells were observed in both control and CGRP-treated animals. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P<0.05). (2) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P<0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P<0.01). AQP4 expression in gastric mucosa was lower in CGRP-treated group than that in control group (P<0.05). bFGF expression in gastric mucosa was higher in CGRP-treated group than that in control group (P<0.01). (3) The mast cell degranulation ratio in control group in gastric mucosa was significantly higher than that in CGRP-treated group (P<0.01). It is concluded that CGRP can regulate the secretion of Gas, SST, AQP(4), and bFGF, inhibit mast cell degaranulation and thus alleviate the damage of gastric mucosa induced by cerebral ischemia and reperfusion. CGRP may be one of the good candidates of potential clinical therapy drugs for regulating gastric mucosal protection and maintaining gastric mucosal integrity after cerebral ischemia and reperfusion.
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PMID:The protective effects of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats. 1990 Apr 92


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