Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin (PG) E1 is a potent vasodilator on the peripheral vessels and also has an inhibitory action of platelet aggregation. Lipo PGE1, the lipid emulsified PGE1 has much longer half life time in the circulation than PGE1 which is rapidly inactivated in the lung. The purpose of this investigation was to study the clinical and hemodynamic effect of Lipo PGE1 on the 15 patients with acute or subacute focal cerebral ischemia. Of these patients, five had evidence of internal carotid artery occlusion, and ten had either occlusion or severe stenosis of middle cerebral artery. Lipo PGE1 containing 15 micrograms of PGE1 was administered within 12 days of onset of ischemic events. Before the first Lipo PGE1 administration, regional cerebral blood flow (rCBF) of the affected middle cerebral artery (MCA) territory was 41.8 +/- 8.4 ml/100 g/min and on the non-affected side was 60.0 +/- 9.4 ml/100 g/min. Immediately after the Lipo PGE1 treatment, rCBF of the MCA region was increased by 6% on the affected side and by 11% on the non-affected side. rCBF of the affected MCA territory was increased more than 15% in five cases (Group 1) and was changed less than +/- 15% in seven cases (Group 2) by the first Lipo PGE1 treatment. Lipo PGE1 was administered every 8 hours for 10 to 14 days in these 12 cases. By the continuous Lipo PGE1 treatment, rCBF of the affected MCA territory increased by 18% in the Group 1 and by 3% in the Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical and hemodynamic effects of lipo PGE1 in cerebral infarction]. 322 65

Prostaglandin (PG) E1 is a potent vasodilator on the peripheral vessels and also has an inhibitory action of platelet aggregation. Thus it is expected that PGE1 may be used for the treatment of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Lipo-PGE1, the lipid emulsified PGE1, is not destroyed in the lung, has much longer half life in the circulation than PGE1 which is rapidly inactivated in the lung. The effects of intravenous injection of lipo-PGE1 on the cerebral hemodynamics and the central conduction time (CCT) of the sensory evoked potential under vasospastic conditions has been studied in eight patients. All these 8 patients demonstrated severe angiographic vasospasm and signs of cerebral ischemia. The 15-20 micrograms of lipo-PGE1 was administered every eight hours for 5 to 7 days. Within 6 hours of the first lipo-PGE1 treatment, the regional cerebral blood flow (rCBF) and the CCT measurements were reported to document the effect of treatment. The average pretreatment of rCBF on the right anterior, middle and posterior cerebral artery were 46.6 +/- 6.8, 56.4 +/- 7.3 and 58.8 +/- 8.9 ml/100 g/min and on the left side were 52.1 +/- 9.2, 49.1 +/- 10.8 and 56.1 +/- 9.2 ml/100 g/min respectively. With treatment these flows increased to 53.0 +/- 6.9, 64.3 +/- 5.3 and 63.0 +/- 4.6 ml/100 g/min respectively on the right side and 60.8 +/- 9.4, 60.6 +/- 9.7 and 60.6 +/- 7.2 ml/100 g/min respectively on the left. The CCT also demonstrated the improvement from 6.36 msec to 6.21 msec by the initial PGE1 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical effects of lipo-prostaglandin E1 in patients with delayed cerebral vasospasm]. 367 May 36

Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascular function. Under normal physiological conditions, PGHS-dependent vasodilators (such as prostacyclin) modulate vascular tone. However, PGHS-dependent vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH(2)) predominates in some vascular pathologies (eg, systemic hypertension, diabetes, cerebral ischemia, and aging). This review will discuss the role of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for treatment of conditions such as chronic inflammatory disease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function.
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PMID:Prostaglandin H synthase and vascular function. 1159 87

Prostaglandin D(2) is the most abundant prostaglandin in the brain. It has long been described as a modulator of the neuroinflammatory process, but little is known regarding the role of its Galpha(s)-coupled receptor, DP1. Therefore, in this study, the effect of the DP1 receptor on the outcome of cerebral ischemia in wildtype (WT) and DP1 knockout (DP1(-/-)) C57Bl/6 mice was investigated. Ischemia-reperfusion injury was produced by a 90-min occlusion of the right middle cerebral artery followed by a 4-day reperfusion. Infarct size was 49.0 +/- 11.0% larger in DP1(-/-) mice (n = 11; P < 0.01) than in WT mice (n = 9 per group). However, no differences were detected in the relative cerebral blood flow (CBF) or any of the physiological parameters measured (n = 5 per group) or in the large blood vessel anatomy (n = 3 per group). To further address whether the DP1 protective role in the brain could be extended to neurons, mouse primary corticostriatal neuronal cultures were exposed to the DP1-selective agonist, BW245C, which provided dose-dependent protection against excitotoxicity induced by glutamate. Protection was significant at a dose as low as 0.05 microm. The results indicate that the DP1 receptor is neuroprotective in both in vivo and in vitro paradigms. Development of drugs to stimulate the DP1 receptor in brain could provide a new therapeutic strategy against cerebral ischemia and potentially other neurological conditions.
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PMID:PGD(2) DP1 receptor protects brain from ischemia-reperfusion injury. 1757 24

Dexmedetomidine (Dexmd), a potent and highly specific alpha(2) adrenoreceptor agonist, is an efficient therapeutic agent for sedation. Dexmd has been recently reported to have a neuroprotective effect. Heat shock protein (HSP) 27, a low-molecular weight HSP has been shown to be expressed following cerebral ischemia in astrocytes but not in neurons. HSP27 expression is involved in ischemic tolerance of the brain. This study investigated the effect of Dexmd on HSP27 in rat C6 glioma cells. 12-O-tetradecanoylphorbol-13-actate (TPA), a direct activator of protein kinase C (PKC), stimulated the phosphorylation of HSP27 at Ser82, but not Ser15 in a time-dependent manner. Prostaglandin (PG) E(1) or PGE(2) which activates the adenylyl cyclase-cAMP system as well as forskolin and dibutyryl-cAMP, suppressed the TPA-induced phosphorylation of HSP27. Dexmd reversed the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system. Therefore, these results strongly suggest that Dexmd reverses the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system activation through the inhibition of its system in C6 cells. alpha(2) Adrenoreceptor agonists may therefore show a neuroprotective effect through the modification of HSP27 phosphorylation induced by PKC activation.
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PMID:Alpha2 adrenoreceptor agonist regulates protein kinase C-induced heat shock protein 27 phosphorylation in C6 glioma cells. 1838 48

Prostaglandin D(2) (PGD(2)) is the most abundant prostaglandin produced in the brain. It is a metabolite of arachidonic acid and synthesized by prostaglandin D(2) synthases (PGDS) via the cyclooxygenase pathway. Two distinct types of PGDS have been identified: hematopoietic prostaglandin D synthase (H-PGDS) and lipocalin-type prostaglandin D synthase (L-PGDS). Because relatively little is known about the role of L-PGDS in the CNS, here we examined the outcomes in L-PGDS knockout and wild-type (WT) mice after two different cerebral ischemia models, transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent distal middle cerebral artery occlusion (pMCAO). In the tMCAO model, the MCA was occluded with a monofilament for 90 min and then reperfused for 4 days. In the pMCAO model, the distal part of the MCA was permanently occluded and the mice were sacrificed after 7 days. Percent corrected infarct volume and neurological score were determined after 4 and 7 days, respectively. L-PGDS knockout mice had significantly greater infarct volume and brain edema than did WT mice after tMCAO (P<0.01). Similarly, L-PGDS knockout mice showed greater infarct volume and neurological deficits as compared to their WT counterparts after pMCAO (P<0.01). Using the two models enabled us to study the role of L-PGDS in both early (tMCAO) and delayed (pMCAO) ischemic processes. Our findings suggest that L-PGDS is beneficial for protecting the brain against transient and permanent cerebral ischemia. These results provide a better understanding of the role played by the enzymes that control eicosanoid synthesis and how they can be utilized as potential targets to prevent damage following either acute or potentially chronic neurological disorders.
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PMID:Lipocalin-prostaglandin D synthase is a critical beneficial factor in transient and permanent focal cerebral ischemia. 1925 53

The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D(2) and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-D: -aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. Moreover, since the elderly are more vulnerable to stroke-related damage than are younger patients, we tested the susceptibility of aged DP1 knockout (DP1(-/-)) mice to brain damage. We found that intrastriatal injection of 15 nmol NMDA caused significantly larger lesion volumes (27.2 +/- 6.4%) in young adult DP1(-/-) mice than in their wild-type counterparts. Additionally, intracerebroventricular pretreatment of wild-type mice with 10, 25, and 50 nmol of the DP1-selective agonist BW245C significantly attenuated the NMDA-induced lesion size by 19.5 +/- 5.0%, 39.6 +/- 7.7%, and 28.9 +/- 7.0%, respectively. The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion-induced brain infarction size significantly (21.0 +/- 5.7%). Interestingly, the aggravated NMDA-induced brain damage was persistent in older DP1(-/-) mice as well. We conclude that the DP1 receptor plays an important role in attenuating brain damage and that selective targeting of this receptor could be considered as an adjunct therapeutic tool to minimize stroke damage.
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PMID:Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice. 2064 May 51