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M Plotkine

Publications and source records attributed to M Plotkine.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1977

[Increase in the oxygen available to the cerebral cortex after the administration of carbonic anhydrase inhibitors].

Oxygen tension (pO2) in cerebral cortex was measured by polarographic method in unanesthetized rabbits. Intravenous administration (25 mg/kg) of carbonic anhydrase inhibitors (acetazolamide, methazolamide, dichlorphenamide, sulthiame) induced an early important rise of cortical p O2, which is not dependent on increase of p O2 and p CO2 and decrease of pH in arterial blood. High dosage of acetazolamide (250 mg/kg) produced the same effect and did not suppress the increase of cortical p O2 under air-CO2 inhalation. This result suggests that CO2 might act specifically upon cerebral vessels.

Animals↗
PubMedDate not supplied

Model of global forebrain ischemia in the unanesthetized rat.

Global forebrain ischemia was induced in unanesthetized rats by electrocauterization of the vertebral arteries and transient occlusion of the common carotid arteries for 30 minutes. Local cerebral blood flow (l-CBF), cortical tissular pO2 (tpO2), electrocorticogram (ECoG), mean arterial pressure, pH and blood gas determinations and neurologic deficit were evaluated during and after ischemia. Cerebral ischemia induced a substantial decrease in l-CBF and tpO2 and the ECoG was flattened. One hour after ischemia, the neurologic deficit was at its maximum, l-CBF was still decreased and ECoG depressed. Twenty-four hours later, the neurologic deficit was still present but ECoG, l-CBF and tpO2 had returned to their preischemic values. Treatments with naloxone were performed during, after or during and after ischemia. When naloxone was administered during or after ischemia, postischemic neurologic deficit was not influenced by the treatment. A slight but significant improvement of the neurologic score was observed when naloxone was injected during ischemia and infused thereafter. Our results show that this experimental model of cerebral ischemia is suitable for quantification of neurologic alterations during the postischemic period. The slight improvement observed with naloxone suggests that endogenous opioids may have a minor role in the neurologic consequences of ischemia.

Animals↗
PubMedDate not supplied

Effect of indomethacin on the coupling of cerebral blood flow to brain metabolism.

The effect of indomethacin (10 mg.kg-1 i.p.) on frontal cerebral blood flow has been investigated in male Sprague Dawley rats using the hydrogen clearance technique. Indomethacin elicited a marked reduction in cerebral blood flow in awake free-moving animals. The response to indomethacin was prevented by pretreatment with pentobarbital (50 mg X kg-1, i.p.). On the other hand, indomethacin was able to antagonize the cerebral vasodilation due to apomorphine chlorhydrate (2 mg X kg-1, i.p.), dexamphetamine tartrate (3 mg X kg-1, i.p.) or immobilization stress. Taken together, the above results lead to the suggestion that indomethacin can suppress the coupling of cerebral blood flow to brain metabolism. Further investigations are needed to ascertain whether this uncoupling influence is related to brain cyclooxygenase inhibition.

Anesthesia↗