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M Plotkine

Publications and source records attributed to M Plotkine.

At least 37 records · Page 2Linked to original sources
PubMed1992

Striatal protection induced by lesioning the substantia nigra of rats subjected to focal ischemia.

Unilateral 6-hydroxydopamine lesion of the substantia nigra reduced the volume of striatal necrosis and suppressed the increase in extracellular glutamate concentration in the striatum induced by middle cerebral artery occlusion in rats. These results indicate that the dopaminergic nigrostriatal pathway is highly involved in the vulnerability of the striatum to ischemia and suggest that glutamate-dopamine interactions may play a key role in the striatal ischemic insult.

Animals↗
PubMed1992

The neuroprotective effect of a nitric oxide inhibitor in a rat model of focal cerebral ischaemia.

Recent data showed that glutamate toxicity in primary cortical cultures is mediated by nitric oxide. In order to investigate the effect of inhibition of NO synthase on focal cerebral ischaemia in rats, we studied the histological consequences of a middle cerebral artery (MCA) occlusion after post-operative treatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. We found a significant reduction of cortical (-43%) and striatal (-25%) necrotic volumes induced by MCA occlusion, indicating that NO synthesis plays an important role in the neurotoxic cascade leading to neuronal damage after focal cerebral ischaemia in rats.

Amino Acid Oxidoreductases↗
PubMed1992

Neurological and behavioral outcomes of focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats. METHODS: We induced permanent occlusion of the left middle cerebral artery in 14 Sprague-Dawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage. RESULTS: Ischemia induced large infarcts in the cortex (138.6 +/- 8.5 mm3) and caudate-putamen (48.8 +/- 2.6 mm3) and, compared with sham-operated rats, produced a dramatic neurological deficit (p less than 0.001) characterized by sensorimotor dysfunctions and hemiplegia. Memory retention was significantly (p less than 0.05) impaired in the passive avoidance task, but neither vigilance and exploratory behavior measured in the modified open-field test nor working memory evaluated in the Y maze test were disturbed. Infarct size was not correlated with the neurological or behavioral deficits. CONCLUSIONS: This lack of correlation indicates the necessity of carrying out parallel histological, neurological, and behavioral studies in any assays of new drugs using this model of focal ischemia.

Animals↗
PubMed1992

[Experimental antithrombotic activity of oral isosorbide dinitrate].

The activity of isosorbide dinitrate (ISDN) a nitrate derivative with platelet anti-aggregant properties, was studied on a model of arterial thrombosis by electric stimulation of the rat carotid arteries. In control animals, occlusive thrombosis occurred in 15.3 +/- 1.0 minutes. When administered orally in dosages of 1 to 30 mg/kg, 30 minutes before stimulation, ISDN prolonged the time to arterial occlusion by a factor of 2 to 3 times. This effect was significant from doses of 1 mg/kg. This anti-thrombotic activity was unchanged by pretreatment of 100 mg/kg I.V. of acetylsalicylic acid, a dose sufficient to inhibit prostacycline synthesis. On the other hand, its activity was completely blocked by the administration of an inhibitor of NO-synthetase, L-nitroarginine methylester (1 mg/kg I.V.). These results show that ISDN is active on a model of arterial thrombosis in the rat by a mechanism independent of prostacycline production but implying a stimulation of the formation of nitric oxide.

Administration, Oral↗
PubMed1991

Enhancement of endogenous excitatory amino acids by theophylline does not modify the behavioral and histological consequences of forebrain ischemia.

The neuroprotective role of endogenous adenosine during forebrain ischemia elicited by 4-vessel occlusion in rats was assessed using the adenosine antagonist, theophylline (32 mg/kg). Despite an increase in the release of glutamate in the hippocampus during ischemia, theophylline did not alter the neurological and histological outcomes. These results indicate that endogenous adenosine does not act as an endogenous neuroprotector by modulating glutamate release in this model.

Adenosine↗
PubMed1991

Nigrostriatal pathway modulates striatum vulnerability to quinolinic acid.

This study evaluates the modulation of striatum vulnerability to quinolinic acid (QA) by the nitrostriatal projection. Unilateral lesioning of the substantia nigra with 6-hydroxydopamine markedly reduced the volume of striatal necrosis observed 3 days after local injection of quinolinic acid (150 nmol). This result is consistent with the concept that the nigrostriatal pathway potentiates the vulnerability of striatum to excitotoxic damage.

Animals↗
PubMed1991

Oral administration of isosorbide dinitrate inhibits arterial thrombosis in rats.

The effect of isosorbide dinitrate, a nitrovasodilator known to inhibit platelet function, was examined in a model of electrically induced carotid artery thrombosis in rats. In the dose range of 1-30 mg/kg isosorbide dinitrate, administered orally, significantly delayed carotid occlusion. These results demonstrate that isosorbide dinitrate has antithrombotic activity and it is suggested that this antithrombotic activity is due to the generation of nitric oxide.

Administration, Oral↗
PubMed1990

Kynurenic acid antagonizes hippocampal quinolinic acid neurotoxicity: behavioral and histological evaluation.

In the present study, we evaluate the ability of kynurenic acid to protect hippocampal neurons from the neurotoxicity of the N-methyl-D-aspartate (NMDA) agonist quinolinic acid. Bilateral intrahippocampal injection of quinolinic acid (120 nmol) led to severe behavioral disturbances and total loss of hippocampal neurons. Intrahippocampal co-injection of kynurenic acid (360 nmol) completely prevented cell loss and behavioral disturbances. However, the protection was incomplete when kynurenic acid was intraperitoneally injected (500 mg/kg, repeated during 4 days). These above results indicate that kynurenic acid can antagonize the neuronal degeneration mediated by excessive stimulation of NMDA receptors in vivo.

Animals↗
PubMed1990

Effects of transient cerebral ischemia on the hippocampal dentate theta (theta) profile in the acute rat: a study 4-5 months following recirculation.

This study mainly describes the long-term effects of 20 min of cerebral ischemia on the profile of the presumed cholinergic theta rhythm in the rat dorsal hippocampal formation during ether anesthesia and injection of the muscarinic agonist agent arecoline. The experimental data were collected 4-5 months after ischemia. They show that ischemia results in a statistically significant reduction in both superficial and deep theta recorded from the CA1 area of the hippocampus and the dentate gyrus, respectively. Amplitude reduction is similar for both rhythms and co-varies positively with the extent of CA1 stratum pyramidale damage which, from light microscope observation, appeared to be the major neuroanatomical consequence of ischemic insult in the dorsal hippocampal formation. The medial septal nucleus-diagonal band of Broca complex involved in theta generation did not suffer visible anatomical damage. Moreover, no significant alteration in the spatial distribution and the density of hippocampal dentate acetylcholinesterase reaction product was seen in ischemic animals. These histological data were statistically confirmed by computerized image analysis. Finally, this is the first investigation to show that transient interruption of cerebral blood flow results in a long-lasting alteration of theta rhythm which is probably the major aspect of the basic activity of the hippocampal formation. Thus, the present findings obtained in the acute rat at 4-5 months postischemia confirm and extend, in most respects, our previous results collected in the chronic animal 2-29 days following 4-vessel occlusion. Possible significance of these findings for the hypothesis of the dependent generation sites of superficial and deep thetas in the hippocampus assumed to be crucial in learning and memory, is discussed.

Acetylcholinesterase↗
PubMed1990

Effect on cerebral blood flow of orally administered indomethacin-loaded poly(isobutylcyanoacrylate) and poly(DL-lactide) nanocapsules.

Nanocapsules, containing indomethacin, were prepared either by interfacial polymerization of isobutylcyanoacrylate monomers or by interfacial deposition of a performed (DL-lactide) polymer. In-vitro release of indomethacin from nanocapsules was dependent on the pH of the sink solution and was enhanced by addition of albumin. A decrease in cerebral blood flow was noted 15 min after oral administration to rats of indomethacin nanocapsules (5 mg kg-1) and lasted over 3 h. Empty nanocapsules had no effect. Since release of indomethacin from nanocapsules is unlikely to occur in the lumen of the stomach, due to unsuitable pH conditions, and nanocapsules have been previously shown to be able to cross the intestinal barrier, to reach the villi vessels intact and to protect against the ulcerating effect of the free drug, it is suggested that the rapid onset of the pharmacological effect was sufficiently induced by free indomethacin released in the plasma following absorption of the intact nanocapsules.

Administration, Oral↗
PubMed1988

Investigations on the role of arachidonic acid metabolism pathways in the antithrombotic activity of nafazatrom and molsidomine.

The activity of nafazatrom and molsidomine, two antithrombotic drugs claimed to increase prostacycline level, was investigated in an electrically-induced carotid thrombosis model in the conscious rat. Both nafazatrom (5 mg/kg, i.v.) and molsidomine significantly delayed thrombus formation, an activity that was shared by prostacyclin (100 ng/kg/min, i.v.). Acetylsalicylic acid, at a dosage devoided of antithrombotic activity (100 mg/kg, i.v.) abolished the effect of nafazatrom but not of molsidomine. These results indicate that a cyclooxygenase-dependent compound (prostacyclin ?) play a major role in the antithrombotic effect of nafazatrom but not of molsidomine. Moreover, since compounds inhibiting the lipoxygenase pathway, i.e., BW755c (10 and 25 mg/kg, i.v.) and nordihydroguaiaretic acid (10 and 25 mg/kg, i.v.) were unable to show any antithrombotic effect, the activity of molsidomine can unlikely be due to its lipoxygenase inhibitory property.

Animals↗
PubMed1987

Electrically induced arterial thrombosis model in the conscious rat.

Thrombus formation was electrically induced in the left common carotid artery of rats with preoccluded both vertebral and right carotid arteries. Following thrombus induction, animals became unresponsive and lost their righting reflex. The loss of righting reflex was observed when cortical tissular pO2 reached 55 +/- 9% of its initial value. A similar decrease in pO2 was induced by mechanical occlusion of the left carotid artery. The delay between discontinuation of current and the loss of righting reflex was measured to indirectly evaluate occlusive thrombus formation. The capacity of various antithrombotic agents to delay the righting reflex loss was studied. Heparin, ticlopidine and the thromboxane-endoperoxides receptor blocker, BM 13177, exerted a significant activity, whereas acetylsalicylic acid and the thromboxane synthetase inhibitors, OKY O46 and dazmegrel, were inefficient.

Animals↗
PubMed1986

Naloxone effect on the neurological deficit induced by forebrain ischemia in rats.

The effect of naloxone upon neurologic deficit was evaluated in a model of transient forebrain ischemia in rats. Awake male Wistar rats were subjected to a 30 minute ischemia by occluding both common carotid arteries 8 days after cauterizing vertebral arteries. Administration of naloxone 1 or 5 mg/kg iv 10 minutes after carotid occlusion or 1 mg/kg iv one hour after clamp removal failed to reduce immediate and tardive neurologic postischemic deficits. On the other hand, in rats treated by a dose of 1 mg/kg naloxone 10 minutes after carotid occlusion and perfused with an additional dose of 2 mg/kg/h for 80 minutes, neurologic score was improved one hour after ischemia. However mortality was not decreased whatever was the modality of naloxone administration. This result confirms previous data showing that naloxone exerts a protective effect when given at sufficiently high dosage.

Animals↗
PubMed1985

Possible non-involvement of lipoxygenase pathway in the cerebral blood flow decrease due to indomethacin.

Indomethacin (10n mg/kg i.p.) induced a marked decrease in local cerebral blood flow (l.CBF), which was measured in the frontal cortex of unanesthetized rats by the hydrogen clearance technique. Brain prostaglandins (PGD2, PGE2, PGF2 alpha,) and 6kPGF1 alpha the stable metabolite of prostacyclin, were significantly decreased. Treatments with inhibitors of lipoxygenase (BW 755C and nordihydroguaiaretic acid) and with FPL 55712, a leukotriene receptor antagonist, did not influence the effect of indomethacin on 1.CBF. The results suggest that the release of vasoconstrictory leukotrienes does not play a major role in the lowering of 1.CBF by indomethacin.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1982

Effect of indomethacin in experimental cerebral ischemia.

The effect of indomethacin treatment (4 mg/kg-1, i.v.) on the cerebrocortical post-ischemic reperfusion ischemia (rabbits) or to focal epicerebral ischemia (cats). When administered prior to global ischemia (but not after), indomethacin enhanced the cortical post-ischemic blood flow. No improvement, however, could be observed in the electrocorticogram in either case. Moreover, indomethacin pretreatment did not change the evolution of the cortical tissular pO2 following focal ischemia. It is suggested that, in spite of post-ischemic amelioration of blood flow, indomethacin is unable to improve tissular oxygenation and electrical activity of the cerebral cortex.

Animals↗
PubMed1981

Recovery from global cerebral ischemia in rabbits: influence of indomethacin.

A 10-min cerebral ischemia was induced in rabbits by a combination of vascular occlusion (carotid and vertebral arteries) and systemic hypotension. Cerebral cortex blood flow, cortical pO2, arterial pH, arterial blood gases, arterial pressure and electrocorticogram were recorded before, during and for 4 h after ischemia. Indomethacin (4 mg . kg-1 i.v.) was administered 45 min before or immediately after ischemia. Pretreatment with indomethacin improved cortical reperfusion but did not influence cortical pO2 and electrocorticographic activity. Post-ischemic treatment did not affect the different measurements. Water and electrolyte contents remained unchanged.

Animals↗
PubMed1981

hypobaric hypoxia: central catecholamine levels and cortical PO2 and avoidance response in rats treated with apomorphine.

The learning of a conditioned avoidance response, the catecholamine levels in some cerebral structures, and the evolution of the cortical PO2, were studied under hypobaric hypoxia (300 torr) and under normoxia, in rats treated or not with apomorphine, at the dose of 1 or 10 mg/kg i.p. Apomorphine at 1 mg/kg improves the learning capacity and stabilises the cerebral catecholamine levels under hypoxia; no modification of the evolution of the cortical PO2 during hypoxia was observed between control rats and rats treated with this dose of apomorphine. Apomorphine at 10 mg/kg totally inhibits learning under normoxia or hypoxia. It is therefore possible to suppose that the antihypoxic protective mechanism of low-dose apomorphine is due to a stabilization of the levels of both dopamine and noradrenaline during hypoxia, but not to an increase in the cerebral oxygen availability. These data suggest the clinical possibility of using other dopaminergic stimulating agents for their eventual antihypoxic properties.

Air Pressure↗