Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nimodipine and dimethyl sulfoxide (DMSO) were tested (alone and in combination) regarding their ability to increase hypoxic tolerance of brain slices under 'hypoxic' (deprivation of oxygen) or 'ischemic' (hypoxia+withdrawal of glucose) conditions. Direct current (DC) and evoked potentials were recorded in the CA1 region of hippocampal slices of adult guinea pigs. After induction of hypoxia or ischemia, the latency of anoxic terminal negativity (ATN) of the DC potential was determined during superfusion with artificial cerebrospinal fluid alone (aCSF), and during superfusion with aCSF containing DMSO [0.1% (14.1 mmol/l) and 0.4% (56.3 mmol/l)] with the addition of nimodipine (40 micromol/l). Latencies of ATN with first hypoxia were 6.7+/-3.7 min in the control group, 9. 3+/-4.2 min in the 0.4% DMSO group and 12.3+/-5.5 min (P=0.007) in the nimodipine/0.4% DMSO group. Latencies of ATN with first ischemia were 2.9+/-2 min in the control group, 4.1+/-1.6 min in the 0.1% DMSO group, 7.1+/-3.9 min in the 0.4% DMSO group (P=0.006), 5.3+/-1. 5 min in the nimodipine/0.1% DMSO group and 7.6+/-3 min (P<0.001) in the nimodipine/0.4% DMSO group. DMSO (0.4%), either alone or in combination with nimodipine, increase the latency of the ATN after acute onset of hypoxia and ischemia.
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PMID:Acute protective effect of nimodipine and dimethyl sulfoxide against hypoxic and ischemic damage in brain slices. 1113 21

Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen accumulation in the basement membrane of aging spontaneously hypertensive stroke-prone rats. The ratio of cortical capillaries with such vascular pathology occurred significantly more frequently in hypertensive animals. Nimodipine and nifedipine are potential drugs to decrease blood pressure in hypertension but their beneficial effects in experimental studies reach beyond the control of blood pressure. Nimodipine and nifedipine can alleviate ischemia-related symptoms and improve cognition. These drugs differ in that nifedipine, but not nimodipine reduces blood pressure at the here-used concentration while both drugs can penetrate the blood-brain barrier. Here we show that chronic treatment of aging hypertensive stroke-prone rats with nimodipine or nifedipine could preserve microvascular integrity in the cerebral cortex.
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PMID:Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain. 1118 80

Excessive calcium influx has been implicated in the pathophysiology of ischemic cerebral damage. The effects of nimodipine, a calcium antagonist, on the Na(+)-K+/MG+2 ATPase activity, Ca+2/Mg+2 ATPase, lipid peroxidation, and early ultrastructural findings were examined at the acute stage of ischemia in the rat brain. Ischemia was produced by permanent unilateral occlusion of the middle cerebral artery. In Group I, the rats which had no ischemia and not received medication were used for determining Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, the extent of lipid peroxidation by measuring the malondialdehyde content and normal ultrastructural findings. In Group II, the rats which had only subtemporal craniectomy without occlusion and received saline solution were used for determining the effect of the surgical procedure on the biochemical indices and ultrastructural findings. In Group III, the rats received saline solution following the occlusion in the same amount of nimodipine and in the same duration as used in Group IV. In Group IV, nimodipine pre-treatment 15 min before occlusion (microgram kg-1 min-1 over a 10 min period) was applied i.v. Na(+)-K+/Mg+2 ATPase and Ca+2/Mg+2 ATPase activities decreased significantly and promptly as early as 10 min and remained at a lower level than the contralateral hemisphere in the same group and at the normal level in Group I. Nimodipine pre-treatment immediately attenuated the inactivation of Na(+)-K+/Mg+2 ATPase (p < 0.05) but there was no change on Ca+2/Mg+2 ATPase activity (p < 0.05). Malondialdehyde content increased significantly in Group III following ischemia as early as 30 min. Nimodipine pre-treatment decreased the malondialdehyde level in Group IV (p < 0.05). This study supports the possibility that nimodipine pre-treatment effects the membrane stabilizing properties via inhibiting the lipid peroxidation and subsequently restoring some membrane bound and lipid dependent enzymes' activity such as Na(+)-K+/Mg+2 ATPase and the ultrastructural findings.
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PMID:The effects of the pre-treatment of intravenous nimodipine on Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat. 1121 Apr 40

Nimodipine, a dihydropyridine calcium entry blocker, has been shown to protect from neuronal damage due to ischemia by providing for increased postischemic perfusion. Further, it has also been demonstrated to have antiepileptic properties. These two properties--calcium channel blockade and anticonvulsant benefits have been applied with success to mood disorder treatment. Although found helpful nearly a decade ago for uncomplicated mania, nimodipine may have particular benefits for those diagnostic subclasses of bipolar disorder most resistant to therapy, e.g., ultra-rapid-cycling bipolars and brief recurrent depressions.
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PMID:The use of nimodipine in the treatment of mood disorders. 1125 83

The present study evaluated the effect of dl-3-n-butylphthalide(NBP), a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO), producing permanent focal ischemia in the right cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements, and the sodium, potassium concentrations with ion-selective electrodes. In this model, NBP at the dose of 80, 160 and 240 mg/kg p.o. 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry, sodium accumulation and potassium loss. Nimodipine treatment (5 mg/kg s.c.) also reduced brain edema (P < 0.05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.
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PMID:Effect of dl-3-n-butylphthalide on brain edema in rats subjected to focal cerebral ischemia. 1132 93

We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of Ca2+ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that Ca2+ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.
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PMID:Cardiovascular responses and nitric oxide production in cerebral ischemic rats. 1243 8

OBJECTIVE: To develop a novel technique of optical recording and its validation for assessment of the neuroprotective effect of nimodipine, a L-type calcium channel blocker. METHODS: In vitro ischemia was induced by oxygen/glucose deprivation (OGD), the light transmittance (LT) of rat hippocampal slices undergoing OGD and reperfusion was quantitated using a simple apparatus relying on basic principles of light transmittance and a computerised image analysis system. RESULTS: OGD was associated with increased LT in the stratum radiatum of CA1 area and the dentate gyrus in hippocampal slices. Peak LT occurred (7.59 +/-1.42) min after OGD, followed by a marked decrease in LT (n=15 slices). Nimodipine administration (0.5 &mgr;mol/L, n=10 slices, 5 &mgr;mol/L, n=9 slices) appeared to protect the tissue from OGD damage by inhibiting elevation of LT, However, 50 &mgr;mol/L nimodipine resulted in increased LT (25.83 +/-6.32). min after administration (n=11 slices). CONCLUSION: LT signal measurement is a non-invasive, reliable method for determination of neuronal damage in ischemic rat brain slices Nimodipine is demonstrated opposite neuroprotective effects depending on its dose.
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PMID:[Optical recording method for evaluation of neuronal damage in rat hippocampal slices during ischemia and reperfusion] 1253 68

Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species with consequent reperfusion injury. Chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries in rats is associated with behavioral and histopathological alterations. Nimodipine, a dihydropyridine calcium channel antagonist, has potent vasodilatory effect on cerebral vessels and increases cerebral blood flow. We analyzed whether nimodipine reduces injury caused by transient forebrain ischemia and long-term cerebral hypoperfusion. Bilateral common carotid occlusion for 30 min followed by 45 min reperfusion resulted in a two-fold increase in lipid peroxidation and superoxide dismutase activity. Nimodipine pretreatment (4 mg/kg, i.p.) brought down these levels by 30 and 23%, respectively. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness (open field paradigm) accompanied by deficits of learning and memory (Morris' water maze testing). Additionally, histopathological observation in hypoperfused brains revealed reactive changes in the form of perivascular inflammation, gliosis and astrocytosis. Nimodipine treatment significantly alleviated these changes in behavioral and histopathological parameters. Our data confirm the protective role of nimodipine in ischemia reperfusion injury. Moreover, it suggests the beneficial role of nimodipine in cerebrovascular insufficiency states and dementia.
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PMID:Nimodipine attenuates biochemical, behavioral and histopathological alterations induced by acute transient and long-term bilateral common carotid occlusion in rats. 1464 94

Despite widespread investigational and clinical usage of the calcium channel blocker nimodipine, its effects on cerebral physiology in normal and ischemic brain remain poorly understood. In order to gain insight into this subject we examined the effects of nimodipine on glucose metabolism and cerebral blood flow-metabolism coupling in the rat during conditions of reproducible focal ischemia. Nimodipine-treated animals were then matched with vehicle-treated controls for both study conditions. Animals were subjected to permanent occlusion of the middle cerebral artery (MCA) along with occlusion of the common carotid arteries. Five minutes into ischemia, an intravenous infusion of nimodipine (1 micro g/kg per min, n=9) or vehicle ( n=9) was initiated and continued until the end of the study. Seventy-five minutes after the occlusion, [14C]2-deoxyglucose was injected into the venous catheter for the measurement of the local cerebral metabolic rate for glucose (LCMRgl), followed 25 min later by the injection of N-isopropyl-[123I] p-iodoamphetamine for the measurement of local cerebral blood flow (LCBF). The animals were killed at the end of 2 h of ischemia, and the brains were processed for double-labeled autoradiography. In all animals, permanent MCA occlusion produced significant decrements in LCBF, LCMRgl, and LCBF/LCMRgl ratio in both the core of the ischemia as well as regions peripheral to the ischemia within the same cerebral hemisphere when compared with non-ischemic brain. There were no significant differences between the nimodipine-treated and vehicle-treated groups. In conclusion, nimodipine does not appear to alter cerebral blood flow or cerebral metabolism in ischemic brain.
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PMID:Nimodipine does not affect the flow-metabolism couple in permanent cerebral ischemia. 1475 81

Delayed cerebral ischemia as a result of cerebral vasospasm is the most common cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH). It leads to death or permanent neurologic deficits in over 17-40% of SAH patients. The initial and main symptom of cerebral vasospasm is diffuse headache and may be accompanied with a slight increase in discomfort from neck stiffness and fever. The clinical diagnosis of cerebral vasospasm is made when the patient experiences an altered level of consciousness or a new focal neurologic deficit. There has been a great progress in identifying the patients at risk, putative mechanisms, and possible treatment options for cerebral vasospasm. However, the problem is by no means solved, mainly due to a limited understanding of the pathologic mechanisms of this complex disease. The iatrogenic factors that can increase the risk of cerebral vasospasm include prolongation of the subarachnoid clot by antifibrinolytic drugs, hypotension, inappropriate treatment of hyponatremia, hypovolemia, hyperthermia and increased intracranial pressure. Nimodipine has been shown to improve neurologic outcome and decrease the incidence of cerebral vasospasm. Triple H therapy is a treatment designed to augment cerebral blood flow for patient with cerebral vasospasm. Hypervolemic hypertension is induced with intravenous volume expansion with crystalloid or colloid to increase cardiac output and raise blood pressure. However, small randomized trials showed no clear benefit. Recently, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators has emerged as the primary intervention for treating medically refractory ischemia from cerebral vasospasm and in many centers is being used as a first-line treatment or even prophylactically. In addition, promising new treatments for cerebral vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia; however, all still need further clinical trials. Newly recognized mediators of cerebral vasospasm after SAH include endothelium-derived mediators, vascular smooth-muscle-derived mediators, proinflammatory mediators involved in blood-brain barrier disruption, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Moreover, observations in the laboratory have, in many circumstances, matched those of reported small series. Larger, prospective, randomized trials are needed to verify several hypotheses of molecular pathophysiology and clinical treatment regimens.
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PMID:Treatment of cerebral vasospasm after subarachnoid hemorrhage--a review. 1567 31


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