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Biomedical subjects

M Plotkine

Publications and source records attributed to M Plotkine.

84 records · Page 5Linked to original sources
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.

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PubMedDate not supplied

[NO synthases: new pharmacological targets in cerebrovascular accident?].

In cerebral ischemia, the disappointment related to anti-glutamate strategies in clinical trials has led to examine new targets for the treatment of stroke. In vitro studies demonstrated that overactivation of glutamate receptors leads to nitric oxide (NO) production that contributes to the excitotoxic neuronal death. The role of NO was then studied in in vivo models of cerebral ischemia. In the early phase after ischemia, NO is produced by the constitutive endothelial and neuronal isoforms of NO-synthase (NOS 3 and NOS 1) while in the later phase, the inducible NOS (NOS 2) is responsible for the delayed production of NO. NOS 3 appears beneficial via vasodilatation and inhibition of leukocyte adhesion and platelet aggregation. By contrast NOS 1 and NOS 2 were demonstrated deleterious in cerebral ischemia. This was shown by three distinct strategies: selective inhibitors, mutant mice deficient in NOS 1 or NOS 2, and antisenses directed to one of these isoforms. Moreover it is now thought that NO-induced neuronal death is mainly mediated through the formation of peroxynitrite anions resulting from the reaction between NO and superoxyde anion. Peroxynitrites indeed damage lipids, proteins and nucleic acids. DNA strand breaks in turn activate poly(ADP-ribose) polymerase (PARP). Overactivation of this enzyme in pathological conditions such as cerebral ischemia seems deleterious by depleting ATP stores. Thus inhibition of the NO-peroxynitrites-PARP pathway may lead to neuroprotective therapeutics in stroke.

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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.

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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↗
PubMedDate not supplied

[Specific assessment of the cerebral and cardiac effects of asphyxic hypoxia. Application to the study of substances with protective activity].

The influence of asphyxia on electrocorticogram (E. Co. G.) and electrocardiogram (E. C. G.) has been studied in curarized rats. The delay between the heightening of the ST component of E. C. G. and the disappearance of E. Co. G. pattern was measured. It provided more useful information on cerebral survival during asphyxia than the only study of E. Co. G. did. This delay was increased (cerebral antihypoxic effect) after intravenous treatment with pyritinol (50 mg/kg), vincamine (5 mg/kg) or propranolol (1 mg/kg), but it was not influenced by pentobarbital (60 mg/kg).

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