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

Idebenone (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone) is a benzoquinone that has been shown to improve cognitive function in animals subjected to cerebral ischemia and in rats with lesions of the basal forebrain cholinergic system. Because the cognitive deficits observed in aged rats have been associated with decreased cerebral blood flow and basal forebrain cholinergic dysfunction, it was hypothesized that IDE might improve cognition in aged animals. In the present study, the effects of idebenone on cognitive function in aged Long-Evans rats were assessed using a battery of tests that evaluated attention, habituation, and spatial learning. Selective attention was assessed using an overshadowing paradigm, where IDE (30 mg/kg, IP) was injected 30 min prior to compound cue exposure. IDE enhanced the overshadowing effect in aged rats. The Morris water maze was used to assess spatial learning, where IDE (3 mg/kg, IP) was injected daily throughout the course of training. IDE did not improve the impaired performance of aged rats in the Morris task. Habituation was tested by measuring recovery from gustatory neophobia. IDE (30 mg/kg, IP) was injected 30 min prior to the first exposure to the novel taste. IDE normalized habituation rate in aged rats. It was concluded that IDE improves some forms of acquisition in aged rats, and may do so by decreasing general reactivity to novel stimuli.
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PMID:Effects of idebenone on information processing in aged Long-Evans rats. 826 97

The goal of the present study was to characterize the effects of chest compression-induced global cerebral ischemia on the hippocampal slice preparation. One of the characteristics of rats exposed to such cardiac arrest is a high susceptibility to sound-induced seizures. We tested audiogenic seizures as an in vivo indicator of ischemic cerebral damage and as a possible small animal model of epilepsy. The results of these tests were reported elsewhere. Long-Evans male rats (200-350 g) were subjected to 7 min of chest compression sufficient to stop the pumping action of the heart. The rats were then revived using cardiopulmonary resuscitation. Evaluation of cerebral damage following cardiac arrest and resuscitation was performed in vitro, by testing neuronal responses to electrical stimulation in hippocampal slices prepared from these animals. Sham control animals were used for comparisons. Twenty-one to 146 days after rats were chest-compressed, hippocampal slices were prepared. Sham control rats, anesthetized but not chest-compressed, were sacrificed one week later for preparation of slices. Rats in a second group exposed to 7-min chest compression, were sacrificed at different time intervals after their resuscitation (from 1 h to 7 days); hippocampal slices were prepared for electrophysiological analysis of neuronal damage. The results of these studies indicate that 3 weeks or longer after chest compression the evoked CA1 population spike amplitude in hippocampal slices was significantly attenuated; in 60% of these slices an epileptiform response was evoked. An increased proportion of slices prepared from rats 1 to 48 h after chest compression showed an augmentation in the amplitude of the evoked population spike; 72 h and up to 7 days after chest compression, an attenuation in the evoked CA1 population spike amplitude was observed, signaling delayed neuronal damage.
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PMID:Cardiac arrest-induced global cerebral ischemia studied in vitro. 884 63

Regional concentrations of leukotriene C4 and extravasation of Evans blue were measured after lateral fluid-percussion brain injury in rats. Tissue levels of LTC4 were elevated in the injured cortex at 10 min, 30 min, and 1 h after injury; these levels returned to normal by 2 h after injury. Increases in the levels of LTC4 were also observed in the ipsilateral hippocampus after brain injury, and these elevations persisted for 2 h after injury. No significant increase in levels of LTC4 was observed in the contralateral cortex at any time after injury. A substantial extravasation of Evans blue was observed only in the ipsilateral cortex and hippocampus at 3 h and 6 h after brain injury. Although a temporal association between LTC4 and blood-brain barrier (BBB) breakdown is suggested by these data, no cause-and-effect relationship has been addressed in this study. However, it is possible that, as is true for cerebral ischemia, LTC4 may play a role as a mediator in the BBB breakdown associated with fluid-percussion brain injury in rats.
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PMID:Regional generation of leukotriene C4 after experimental brain injury in anesthetized rats. 900 63

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
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PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7

Fructose-1,6-bisphosphate has been shown to exert beneficial effects in different experimental models of cerebral ischemia. In view of this evidence, we have determined whether the compound protects the brain during microsphere-induced ischemia. One thousand two hundred microspheres were injected into female rats through a catheter inserted into the right common carotid artery and, 15 minutes and again 24 hours later, we intravenously treated the animals with 333 mg Kg(-1) of fructose-1,6-bisphosphate. The injection of microspheres produced significant changes in the rats' gross behavior, in their performance in the beam walking test, and in their brain lactate concentrations. The treatment with fructose-1,6-bisphosphate significantly attenuated the behavioral alterations induced by microsphere ischemia, but not in reducing brain accumulation of lactate. Moreover, the compound was shown to ameliorate the blood-brain barrier dysfunction, produced 2 and 4 hours after microsphere injection, evaluated by the Evans blue method. These results suggest that fructose-1,6-bisphosphate possesses salutary properties against the damages induced by microsphere ischemia.
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PMID:Effects of fructose-1,6-biphosphate on microsphere-induced cerebral ischemia in the rat. 925 Jul 17

Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.
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PMID:Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia. 938 5

The aim of the present study is to compare the influence of timing and duration of mild hypothermia on rats subjected to 3 h of middle cerebral artery occlusion followed by 72 h of reperfusion. Sixty-four Sprague-Dawley rats were divided into three mild hypothermic groups according to the duration of mild hypothermia (MHT 32 +/- 0.2 degrees C): intra-ischemia (MHTi); intra-reperfusion (MHTr); and intra-ischemia/ reperfusion (MHTi + r). Our control group was normothermic (NT 37 +/- 0.2 degrees C). Reversible focal cerebral ischemia was carried out in rats with a suture technique. Cerebral blood flow was measured by laser Doppler flowmetry to confirm occlusion and reperfusion. The permeability of the blood-brain barrier was determined by the extravasation of Evans's blue dye, and infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining at 72 h after reperfusion. Acute post-ischemic hyperperfusion and delayed hypoperfusion in the ischemic perifocal area and sustained hypoperfusion in the ischemic core were inhibited in MHTi + r and MHTi rats (p < 0.05) as compared to the NT rats. The action of MHTi + r on preventing post-ischemic progressive hypoperfusion in the perifocal area was more effective than that of MHTi 2 h after reperfusion (p < 0.05). Blood-brain barrier disruption in the basal ganglia and cortex areas was significantly reduced in both MHTi + r and MHTi groups, and especially the former. Infarct volume was significantly reduced in both MHTi and MHTi + r groups (p < 0.05). MHTi and MHTi + r have protective effects for reducing ischemia/reperfusion injury. The potential mechanisms may include inhibition of post-ischemic hyperperfusion, and delayed and sustained hypoperfusion.
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PMID:The effect of extending mild hypothermia on focal cerebral ischemia and reperfusion in the rat. 947 Nov 4

We examined the effect of BBB022, a type IV phosphodiesterase inhibitor, on blood-brain barrier (BBB) integrity after transient middle cerebral artery occlusion (MCAo) in rats. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 min of temporary MCAo by retrograde intraluminal insertion of a nylon suture coated with poly-L-lysine. The drug (BBB022 in saline, 1 mg kg-1 h-1, i.v.) or vehicle (0.9% saline, 1-2 ml kg-1 h-1) was administered by infusion after the onset of MCAo. Four animal groups were studied: Groups A and B were treated by infusion of vehicle or drug over 5 h, and groups C and D over 48 h. Damage to the BBB was judged by extravasation of Evans blue (EB) dye, which was administered i.v. at 3 h after the onset of MCAo in groups A and B; and at 46 h in groups C and D. Fluorometric quantitation of EB was performed 1 or 2 h later in six brain regions. In the 5-h infusion series (group B), BBB022 decreased dye extravasation in the ipsilateral cortex, striatum and hemisphere (hemisphere mean+/-S.E.M. : 41.2+/-5.4 vs. 82.4+/-9.2 microg/g, p=0.005) compared to the vehicle-treated group (A). The 48-h infusion of BBB022 (group D) also decreased dye extravasation in the ipsilateral cortex (7.4+/-2. 5 vs. 29.0+/-8.3 microg/g, p=0.05), striatum (17.2+/-2.2 vs. 50. 8+/-12.1 microg/g, p=0.03) and hemisphere (30.7+/-4.0 vs. 93.2+/-18 microg/g, p=0.01) compared to the vehicle-treated group (C). BBB022 also significantly improved the neurological score at 3 and 5 h after MCAo (in the 5-h infusion group) and at 60 min, 24 h and 48 h (in the 48-h infusion group) compared to the vehicle groups. These data indicate that BBB022 prevents ischemic damage to the BBB after focal cerebral ischemia in rats.
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PMID:Protection against blood-brain barrier disruption in focal cerebral ischemia by the type IV phosphodiesterase inhibitor BBB022: a quantitative study. 951 48

In order to understand why exogenous epinephrine decreases the convulsive dose of lidocaine, the authors investigated cerebral circulation and plasma lidocaine concentrations in Wistar rats under general anesthesia. In the first experiment, baseline evaluations of each rat's electroencephalogram (EEG), mean arterial pressure (MAP), regional cerebral blood flow (r-CBF), cerebrospinal fluid (CSF) pressure, and cerebral perfusion pressure (CPP) were made. The rats were then assigned to one of three groups: Group L (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 kg/kg/min); and Group E (n=5) received intravenous epinephrine (2.5 microg/kg/min). Cumulative doses of lidocaine at the onset of EEG spike activity in Groups L and LE were compared. Blood-brain barrier (BBB) permeability was evaluated by observing extravasation of Evans blue (EB) dye. In the second experiment, additional rats were allocated to two treatment groups: Group L' (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE' (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 microg/kg/min). Brain tissue oxygen partial pressure (PtO2) was monitored during infusion, and arterial and sagittal sinus blood samples were obtained immediately after the onset of EEG spike activity to determine plasma lidocaine concentration. The convulsive dose of lidocaine was significantly decreased when lidocaine was administered with epinephrine (Group L: 61.5+/-5.3 mg/kg (mean+/-SD); Group LE: 30.1+/-4.0 mg/kg) (p < 0.05), but there were no significant differences in plasma lidocaine concentration among these groups. R-CBF, CSF pressure, and CPP immediately before EEG spike activity were higher in Group LE than in Group L. Neither decreased PtO2 nor extravasation of EB was observed in rats treated with epinephrine and lidocaine, excluding cerebral ischemia and BBB breakdown from possible mechanisms by which epinephrine decreased the convulsive dose of lidocaine. None of the rats in Group E exhibited EEG findings suggestive of a preconvulsive state, ruling out a convulsive effect of epinephrine itself. The results suggest that an increase in lidocaine supply to the brain caused by increased CBF causes the low cumulative dose of lidocaine at the onset of convulsion in rats given lidocaine plus epinephrine.
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PMID:The effects of exogenous epinephrine on a convulsive dose of lidocaine: relationship with cerebral circulation. 968 7

In this study we sought to determine the optimal brain temperature for treating compression-induced cerebral ischemia. Six cats each were treated with a deep-brain temperature of 37 degrees C (control), 33 degrees C (mild hypothermia), or 29 degrees C (moderate hypothermia). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, as were arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2). The cerebral metabolic rate of oxygen (CMRO2) was calculated. Extracellular glutamate concentration was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero. This ischemia was maintained for 5 min, after which the balloon was deflated. Mild hypothermia showed coupled CBF-metabolic suppression, but moderate hypothermia resulted in disproportionately increased AVDO2, decreased ScvO2, and low CBF/CMRO2 (relative ischemia). Reactive hyperemia after balloon deflation was decreased after both mild and moderate hypothermia, as was the tissue volume showing Evans blue dye extravasation. Extracellular glutamate increased in control animals, an effect most effectively suppressed in the mild hypothermia group. These data favor 33 degrees C as the optimal temperature for treating compression-related cerebral ischemia.
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PMID:Effects of mild and moderate hypothermia on cerebral metabolism and glutamate in an experimental head injury. 977 90


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