Biomedical subjects

M Allix

Publications and source records attributed to M Allix.

12 recordsLinked to original sources

PubMed1992

Inhibition of glutamate release in rat hippocampus by kynurenic acid does not protect CA1 cells from forebrain ischemia.

We assessed the effect of a broad spectrum glutamatergic receptor antagonist, kynurenic acid (500 mg/kg) on ischemia-induced hippocampal glutamate release and neuronal damage. Kynurenic acid significantly decreased glutamate release during ischemia but had no effect on the hippocampal lesion. Some protection was observed in the cortex and in the striatum. These data suggested that the extracellular accumulation of glutamate during forebrain ischemia does not play a major role in the hippocampus.

Animals↗

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

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↗

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↗

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↗