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)

Cerebral infarct (stroke) causes striatal damage with subsequent deterioration of sensorimotor and cognitive functions that may be mediated by the dopamine receptor system. In the present study, transient, focal ischemia was induced in Sprague-Dawley rats by middle cerebral artery occlusion. Ischemic animals exhibited significantly less dopamine antagonist (haloperidol)-induced catalepsy and more dopamine agonist (amphetamine)-induced hyperactivity than sham-operated animals. Younger ischemic animals showed more profound behavioral alteration but also displayed greater recovery over time than older ischemic animals. Histologic data revealed a lateral striatal lesion in all ischemic animals. These results place the striatal dopaminergic system as a possible strategic venue for the treatment of cerebral ischemia. In addition, aging is found to be a risk factor for stroke as noted in humans.
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PMID:Striatal dopamine-mediated motor behavior is altered following occlusion of the middle cerebral artery. 750 69

6-[6-(4-Hydroxypiperidinyl)hexyloxy]-3-methylflavone HCI, (NPC 16377), a potent and highly selective sigma-site ligand, was evaluated in tests predictive of antipsychotic and neuroprotective potential and for toxicity. Like haloperidol, clozapine and remoxipride, and the sigma-ligands BMY 14802, ifenprodil and rimcazole, NPC 16377 reversed amphetamine-induced hyperactivity and apomorphine-induced climbing in mice. Additional evidence for antipsychotic activity was obtained in rats with NPC 16377, clozapine, BMY 14802, ifenprodil, haloperidol and rimcazole, all of which reduced conditioned avoidance responses at doses that did not reduce escape behavior. NPC 16377 did not induce catalepsy in mice, suggesting a decreased liability for producing extrapyramidal side effects. NPC 16377 extended survival time for mice exposed to a hypoxic environment. In a model of global ischemia using conscious gerbils, NPC 16377 prevented damage to hippocampal CA1 neurons after either intraperitoneal or oral administration. NPC 16377 did not disrupt prepulse inhibition or block the disruption of prepulse inhibition induced by the phencyclidine site-selective ligand (+)MK-801. In rats trained to discriminate phencyclidine from saline, NPC 16377 did not substitute for the psychotomimetic. These data are consistent with the notion that selective sigma-agents may possess antipsychotic and neuroprotective activities. Moreover, the results from prepulse inhibition and drug discrimination experiments suggest that NPC 16377 is devoid of phencyclidine-like effects.
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PMID:NPC 16377, a potent and selective sigma-ligand. II. Behavioral and neuroprotective profile. 809 65

The characterization of sensory, motor and cognitive dysfunctions following occlusion of the middle cerebral artery (MCA) is prerequisite to investigations of treatment intervention in animal models of ischemia. Different strategies are used to induce ischemia, but the focal, transient occlusion of the MCA has been reported to result in neuropathology most similar to that seen in clinical cerebral ischemia. If the MCA occlusion technique results in a stroke animal model, then the behavioral impairments inherent in stroke should be manifested in this model. The present study provides a further characterization of behavioral alterations associated with MCA occlusion. Sprague-Dawley rats underwent temporal occlusion of the right MCA, and at 1 mo and 2 mo postischemia, were subsequently tested in passive avoidance behavior, motor coordination, asymmetrical motor behavior, neurological functioning, nocturnal spontaneous and amphetamine-induced locomotor activity, and haloperidol-induced catalepsy. Results revealed that ischemic rats showed long-term impairments in sensory, motor and cognitive functions. The discrepancy with other studies reporting temporal MCA-induced behavioral deficits may be due to techniques used to induce ischemia and consequent CNS damage, differences in time period of testing (i.e., immediate vs. later postischemia, nighttime vs. daytime), number of test-retests over the course of the experiment, and age of the animals. The mechanism involved in the MCA-induced behavioral changes may be represented by loss of dopamine receptors on striatal neurons. Histological analysis revealed damage limited to the lateral aspect of the striatum. These behavioral and anatomical data support MCA occlusion as a model of ischemia, and elucidate important factors that should be controlled for in characterizing the MCA-induced neuropathological alterations.
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PMID:Locomotor and passive avoidance deficits following occlusion of the middle cerebral artery. 857 87

Glutamate in the basal ganglia has important roles in the regulation of motor processes and this is the first study on the role of inhibitory, group II, metabotropic glutamate receptors (mGluRs) for motor behaviour. The group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (L-CCG I) dose dependently induced catalepsy, infused intracerebroventricular (i.c.v.) in rats. The catalepsy was antagonised by dizocilpine and D,L-amphetamine, i.e. by N-methyl-D-aspartate receptor blockade and dopamine receptor activation, respectively. Psychotomimetic side effects limit the clinical use of previously suggested postsynaptic approaches to reduce pathological glutamatergic overactivation, as occuring in epilepsy, ischemia or trauma, but group II agonists provide a new presynaptic approach. Since the catalepsy-induction predicts a lack of psychotomimetic side effects, this study indicates that presynaptic approaches on mGluRs may be more suitable in these situations.
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PMID:The mGluRs group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine induces catalepsy in the rat, which is pronouncedly antagonised by dizocilpine and D,L-amphetamine. 975 96

Flupirtine is a triaminopyridine derived centrally acting analgetic, which has been found to display neuroprotective effects in models of excitotoxic cell damage, global, and focal ischemia, but no direct interaction with any component of the N-methyl-D-aspartate (NMDA) and glutamate triggered Ca(2+)-channel. Additionally flupirtine shows potent antioxidant effects in isolated mitochondria and cell culture. Work in models of monoamine depletion and neuroleptic induced catalepsy in rats suggests a interaction of flupirtine with the dopaminergic neurotransmitter system as well. This prompted us to examine the effect of flupirtine on methamphetamine toxicity in mice and to investigate the influence on dopamine release and free radical formation in the rat striatum by microdialysis that may explain methamphetamine neurotoxicity. Pretreatment of C57-BL mice with flupirtine (4 x 10 mg/kg) significantly attenuated the striatal dopamine loss after methamphetamine application (4 x 5 mg/kg). In rats, a single injection of 10 mg/kg flupirtine reduced the methamphetamine induced striatal dopamine release by almost 50%, as measured by in vivo microdialysis. Flupirtine, however, did not influence the increase of free radical formation after methamphetamine infusion, which was assayed after infusion of salicylic acid by quantification of 2,3- and 2,5-dihydroxybenzoic acid. This suggests that other mechanisms rather than dopamine metabolism and autoxidation, may contribute to methamphetamine neurotoxicity.
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PMID:Attenuation of methamphetamine induced dopaminergic neurotoxicity by flupirtine: microdialysis study on dopamine release and free radical generation. 1258 76

Our previous studies revealed that iptakalim, a novel ATP-sensitive potassium channel opener, has a significant neuroprotective function against ischemia in vivo or rotenone-induced neurotoxicity in vitro. To investigate the potential pharmaceutical benefit of ATP-sensitive potassium channel openers on neurodegenerative diseases, we studied the effects of iptakalim and diazoxide, a selective mitochondrial ATP-sensitive potassium channel opener, on the rotenone-induced nigrostriatal degeneration in rats. Iptakalim (1.5 mg/kg/day, orally) or diazoxide (1.5 mg/kg/day, orally) alone was administered to rats for 3 days, and then for 4 weeks was used daily with an injection of rotenone (2.5 mg/kg/day, subcutaneously) 1 hr later each time. The results showed that rotenone-infused rats exhibited parkinsonian symptoms and had dopamine depletion in the striatum and substantia nigra. Pretreatment with iptakalim or diazoxide prevented rotenone-induced catalepsy and the reduction of striatum dopamine contents. Moreover, iptakalim and diazoxide reduced the enzymatic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. These neuroprotective effects of iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. In conclusion, our data suggested that mitochondrial ATP-sensitive potassium channels might play a key role in preventing both parkinsonian symptoms and neurochemistry alterations induced by rotenone in rats. The selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for prevention and treatment of neurodegenerative disorders such as Parkinson's disease.
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PMID:Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats. 1579 34

We investigated the anxiolytic effects Agaricus brasiliensis extract (AbSE) on ischemia-induced anxiety using the plus-maze test and the social interaction test. The animals were treated orally with AbSE (4, 8, and 10 mg/kg/d, respectively) for 30 d, followed by middle cerebral artery occlusion-induced cerebral ischemia. Levels of noradrenaline, dopamine, and serotonin in the cerebral cortex of rats, as well as oxidative stress and plasma corticosterone levels were analyzed, respectively. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders, and the catalepsy test was carried out to investigate whether AbSE induces catalepsy. Our results demonstrate that oral administration of AbSE presented anxiolytic-like effects in the elevated plus-maze test and the social interaction test. Furthermore, AbSE did not induce extrapyramidal symptoms in the catalepsy test. The mechanism underlying the anxiolytic effect of AbSE might be increased brain monoamine levels and plasma corticosterone levels and decreased oxidative stress in cerebral ischemia/reperfusion rats.
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PMID:Anxiolytic Effects of Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Higher Basidiomycetes) on Ischemia-Induced Anxiety in Rats. 2574 1