The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Roger P Simon - One of the best experts on this subject based on the ideXlab platform.
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lesioning of deep Prepiriform Cortex protects against ischemic neuronal necrosis by attenuating extracellular glutamate concentrations
Journal of Neurochemistry, 2002Co-Authors: Kenji Kawaguchi, Michelle Huerbin, Roger P SimonAbstract:Abstract: An area of the deep Prepiriform Cortex is a controlling site for limbic seizures. Focal pharmacologic blockade of NMDA receptors in the deep Prepiriform Cortex protects against hippocampal cell injury during limbic seizures induced by intravenous kainate and during the excitotoxicity of global ischemia. In the current study, the deep Prepiriform Cortex was lesioned bilaterally by microinjection of kainate, 3 days before 10 min of global ischemia induced by four-vessel occlusion. Extracellular glutamate concentrations in the hippocampus were measured before, during, and after global ischemia by using in vivo microdialysis technique. Surviving hippocampal neurons were counted 7 days after ischemia. Lesioned animals showed significantly greater numbers of surviving neurons and significantly lower ischemia-induced elevations of extracellular glutamate concentrations than non-lesioned animals. During seizures induced from the deep Prepiriform Cortex, the immediate early gene cox-2 is expressed in the hippocampus. These results indicate that deep Prepiriform Cortex can be a modulatory site for ischemic hippocampal injury.
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non nmda but not nmda blockade at deep Prepiriform Cortex protects against hippocampal cell death in status epilepticus
Brain Research, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Abstract The present study investigates the role of pharmacologic blockade of NMDA ( N -methyl- d -aspartate) and non-NMDA receptors at deep Prepiriform Cortex (area tempestas, AT) in neuronal injury during prolonged seizures in rat. Status epilepticus was induced by intravenous kainate (15 mg/kg) and neuronal death was assessed in hippocampal CA3 sector 72 h following status epilepticus. Unilateral equimolar microinjections of 2-amino-7-phosphonoheptanoic acid (AP-7), an NMDA receptor antagonist, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F )quinoxaline (NBQX), a non-NMDA receptor antagonist, into AT were given prior to kainate administration. Counts of surviving cells in CA3 ipsilateral to NBQX-injected AT were significantly greater than on the contralateral control-side, but no significant difference between the AP-7-injected and saline-injected side was found. These results indicate that neurotransmission via non-NMDA receptors is more important than that via NMDA receptors at AT in the genesis of neuronal injury in hippocampus during kainate-induced status epilepticus.
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deep Prepiriform Cortex modulates neuronal cell death in global ischemia
Journal of Cerebral Blood Flow and Metabolism, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Deep Prepiriform Cortex has an important role in modulating neurotransmission during limbic seizures. We used pharmacologic blockade of non-N-methyl-D-aspartate (NMDA) receptors to study excitatory circuitry from the deep Prepiriform Cortex to the hippocampus during global ischemia in rat. NBQX, a potent non-NMDA glutamate receptor antagonist, was microinjected stereotactically into the deep Prepiriform Cortex before global ischemia for 10 min. Neuronal cell death in the hippocampus was evaluated quantitatively 72 h after ischemia. The NBQX-injected rats had a greater number of surviving cells in CA1 sector of hippocampus than did saline-injected controls or rats that received NBQX injections 1 mm from the target. Thus, excitatory amino acid-mediated circuitry emanating from deep Prepiriform Cortex modulates ischemic neuronal injury in the hippocampus.
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pharmacologic blockade of non nmda receptors at deep Prepiriform Cortex attenuates heat shock protein expression in global ischemia
Brain Research, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Abstract Deep Prepiriform Cortex modulates excitatory activity in the limbic system during seizures. We therefore studied a potential role for this system in another process involving excitatory neurotransmission: global ischemia in the rat. The non-NMDA antagonist NBQX was microinjected bilaterally into deep Prepiriform Cortex prior to 10 min of global ischemia. Hippocampal cell injury was then assessed by heat shock protein (HSP) expression 24 h after ischemia. NBQX significantly decreased the number of HSP positive cells in both CA1 and CA3 hippocampal subsectors, suggesting the possibility that pathways from deep Prepiriform Cortex to hippocampus modulate excitotoxicity in target neurons during ischemia.
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deep Prepiriform Cortex modulates kainate induced hippocampal injury
Neuroscience, 1994Co-Authors: S Shimosaka, Roger P SimonAbstract:As seizure propagation within limbic structures is mediated in part by a small area of deep Prepiriform Cortex (area tempestas), we investigated the role of area tempestas in modulating hippocampal injury induced by systemic kainate administration. Injury was quantitated by counting the numbers of neurons that stained for the 72,000 mol. wt heat shock protein and with acid-fuchsin dye. Status epilepticus induced these markers of neuronal injury in the CA1 and CA3a regions of the hippocampus, thalamus, piriform Cortex and the amygdaloid complex. Microinjection of 2-amino-7-phosphonoheptanoic acid, a competitive antagonist of the N-methyl-D-aspartate subclass of the glutamate receptor, into area tempestas prior to systemic administration of kainate attenuated both heat shock protein induction and acid-fuchsin labeling in CA1 and CA3a pyramidal neurons without reducing the duration of electrographic seizures. Injections of bicuculline, a GABA antagonist, into area tempestas produced hippocampal damage when given with subcytotoxic doses of intravenous kainate. Thus, area tempestas may be a uniquely sensitive anatomical structure involved not just in seizure propagation but also in modulating the extent and pattern of damage induced in hippocampal neurons as a result of prolonged, systemically induced seizures. These effects are due in part to excitatory and inhibitory projections to neurons in area tempestas.
Thomas F. Murray - One of the best experts on this subject based on the ideXlab platform.
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THE JOURNAL Or PHARYACOLOCY AND EXPERIMENTAL n(ERAPEUTIC8 Adenosine Al Receptor Activation Mediates Suppression of (-)- Bicuculline Methiodide-Induced Seizures in Rat Prepiriform Cortex1
2020Co-Authors: Paul H. Franklin, Ge Zhang, E. D. Tripp, Thomas F. MurrayAbstract:ABSTRACT The protective effects of a series of stable adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide into the rat Prepiriform Cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido-adenosine (NECA), cyclohexyladenosine, cyclopentyladenosine, 2-chloroadenosine and R-and S-phenylisopropyladenosine (R-and S-PIA), protected animals against seizures in a dosedependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses r 6.8 pmol. In contrast, heroic doses of the A, selective ligand, 2-phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA > cyclohexyladenosine > cyclopentyladenosine r R-PIA > 2chloroadenosine > S-PIA 3 Bphenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A, adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA d i i s e s to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodideinduced seizures. These results suggest that adenosine A, receptors may participate in the normal inhib itory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy. The inhibitory effects of adenosine on CNS function are manifold, and a compelling body of evidence now attests to the physiological relevance of these actions. Adenosine exerts its inhibitory influence in the CNS through activation of cell surface receptors a t both pre-and postsynaptic locations, and mechanisms for its synthesis, release and high-affinity uptake have been described in the mammalian CNS Many tissues and organ systems including the CNS contain a t least two classes of membrane-associated adenosine receptors which are coupled with opposing polarities to regulation of adenylyl cyclase activity. Adenosine receptors thus have been classified as A, or A, based on their capacity to inhibit or stimulate the rate of cyclic AMP synthesis, respectively, upon activation by adenosine agonists (Hamprecht and Vancalker, 1985
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the σ receptor ligand 1 3 di 2 tolyl guanidine is anticonvulsant in the rat Prepiriform Cortex
European Journal of Pharmacology, 1993Co-Authors: Jane E Roth, Paul H. Franklin, Thomas F. MurrayAbstract:Abstract Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED 50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (−)-bicuculline methiodide in the rat Prepiriform Cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic σ ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve σ receptors.
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Manipulation of endogenous adenosine in the rat Prepiriform Cortex modulates seizure susceptibility.
The Journal of pharmacology and experimental therapeutics, 1993Co-Authors: Ge Zhang, Paul H. Franklin, Thomas F. MurrayAbstract:A1 adenosine receptors in the rat Prepiriform Cortex play an important role in the inhibition of bicuculline methiodide-induced convulsions. In the present study we evaluated manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the rat Prepiriform Cortex. Administration of exogenous adenosine afforded a dose-dependent protection (ED50 = 48.1 +/- 8.4 nmol) against bicuculline methiodide-induced seizures, and these anticonvulsant effects were significantly potentiated by treatment with an adenosine kinase inhibitor, 5'-amino-5'-deoxyadenosine; by the adenosine transport blockers, dilazep or nitrobenzylthioinosine 5'-monophosphate; and by an adenosine deaminase inhibitor, 2'-deoxycoformycin. When administered alone, 5'-amino-5'-deoxyadenosine, 5'-iodotubercidin and dilazep were found to be highly efficacious as anticonvulsants with respective ED50 values of 2.6 +/- 0.8, 4.0 +/- 2.7 and 5.6 +/- 1.5 nmol. In contrast, 2'-deoxycoformycin was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the central nervous system. The adenosine antagonist, 8-(p-sulfophenyl)theophylline, increased markedly the severity of bicuculline methiodide-induced seizures. Moreover, reduction of extracellular adenosine formation by a focal injection of an ecto-5'-nucleotidase inhibitor, alpha, beta-methyleneadenosine diphosphate, produced generalized seizures (ED50 = 37.3 +/- 22.7 nmol). Together the proconvulsant effect of an adenosine receptor antagonist and the convulsant action of an ecto-5'-nucleotidase inhibitor further support the role of endogenous adenosine as a tonically active antiepileptogenic substance in the rat Prepiriform Cortex.
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dextrorotatory opioids and phencyclidine exert anticonvulsant action in Prepiriform Cortex
European Journal of Pharmacology, 1992Co-Authors: Jane E Roth, Thomas F. Murray, Ge Zhang, Paul H. FranklinAbstract:We have investigated the ability of an array of putative noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists to suppress convulsions induced by a unilateral, focal injection of (−)-bicuculline methiodide (118 pmol) into the rat Prepiriform Cortex. The anticonvulsant potency of these compounds, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801)>dextrorphan ⩾ 1-(1-phenylcyclohexyl)piperidine hydrochloride (PCP)>dextromethorphan > (+)-pentazocine, upon microinjection into the Prepiriform Cortex, was highly correlated (r = 0.971; P < 0.01) with their respectiv affinities for the [3H]dextrorphan-labelled NMDA receptors in rat forebrain membranes. These results suggest that noncompetitive antagonism of NMDA receptors underlies the anticonvulsant action of these compounds.
Kenji Kawaguchi - One of the best experts on this subject based on the ideXlab platform.
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lesioning of deep Prepiriform Cortex protects against ischemic neuronal necrosis by attenuating extracellular glutamate concentrations
Journal of Neurochemistry, 2002Co-Authors: Kenji Kawaguchi, Michelle Huerbin, Roger P SimonAbstract:Abstract: An area of the deep Prepiriform Cortex is a controlling site for limbic seizures. Focal pharmacologic blockade of NMDA receptors in the deep Prepiriform Cortex protects against hippocampal cell injury during limbic seizures induced by intravenous kainate and during the excitotoxicity of global ischemia. In the current study, the deep Prepiriform Cortex was lesioned bilaterally by microinjection of kainate, 3 days before 10 min of global ischemia induced by four-vessel occlusion. Extracellular glutamate concentrations in the hippocampus were measured before, during, and after global ischemia by using in vivo microdialysis technique. Surviving hippocampal neurons were counted 7 days after ischemia. Lesioned animals showed significantly greater numbers of surviving neurons and significantly lower ischemia-induced elevations of extracellular glutamate concentrations than non-lesioned animals. During seizures induced from the deep Prepiriform Cortex, the immediate early gene cox-2 is expressed in the hippocampus. These results indicate that deep Prepiriform Cortex can be a modulatory site for ischemic hippocampal injury.
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non nmda but not nmda blockade at deep Prepiriform Cortex protects against hippocampal cell death in status epilepticus
Brain Research, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Abstract The present study investigates the role of pharmacologic blockade of NMDA ( N -methyl- d -aspartate) and non-NMDA receptors at deep Prepiriform Cortex (area tempestas, AT) in neuronal injury during prolonged seizures in rat. Status epilepticus was induced by intravenous kainate (15 mg/kg) and neuronal death was assessed in hippocampal CA3 sector 72 h following status epilepticus. Unilateral equimolar microinjections of 2-amino-7-phosphonoheptanoic acid (AP-7), an NMDA receptor antagonist, or 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F )quinoxaline (NBQX), a non-NMDA receptor antagonist, into AT were given prior to kainate administration. Counts of surviving cells in CA3 ipsilateral to NBQX-injected AT were significantly greater than on the contralateral control-side, but no significant difference between the AP-7-injected and saline-injected side was found. These results indicate that neurotransmission via non-NMDA receptors is more important than that via NMDA receptors at AT in the genesis of neuronal injury in hippocampus during kainate-induced status epilepticus.
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deep Prepiriform Cortex modulates neuronal cell death in global ischemia
Journal of Cerebral Blood Flow and Metabolism, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Deep Prepiriform Cortex has an important role in modulating neurotransmission during limbic seizures. We used pharmacologic blockade of non-N-methyl-D-aspartate (NMDA) receptors to study excitatory circuitry from the deep Prepiriform Cortex to the hippocampus during global ischemia in rat. NBQX, a potent non-NMDA glutamate receptor antagonist, was microinjected stereotactically into the deep Prepiriform Cortex before global ischemia for 10 min. Neuronal cell death in the hippocampus was evaluated quantitatively 72 h after ischemia. The NBQX-injected rats had a greater number of surviving cells in CA1 sector of hippocampus than did saline-injected controls or rats that received NBQX injections 1 mm from the target. Thus, excitatory amino acid-mediated circuitry emanating from deep Prepiriform Cortex modulates ischemic neuronal injury in the hippocampus.
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pharmacologic blockade of non nmda receptors at deep Prepiriform Cortex attenuates heat shock protein expression in global ischemia
Brain Research, 1997Co-Authors: Kenji Kawaguchi, Roger P SimonAbstract:Abstract Deep Prepiriform Cortex modulates excitatory activity in the limbic system during seizures. We therefore studied a potential role for this system in another process involving excitatory neurotransmission: global ischemia in the rat. The non-NMDA antagonist NBQX was microinjected bilaterally into deep Prepiriform Cortex prior to 10 min of global ischemia. Hippocampal cell injury was then assessed by heat shock protein (HSP) expression 24 h after ischemia. NBQX significantly decreased the number of HSP positive cells in both CA1 and CA3 hippocampal subsectors, suggesting the possibility that pathways from deep Prepiriform Cortex to hippocampus modulate excitotoxicity in target neurons during ischemia.
Paul H. Franklin - One of the best experts on this subject based on the ideXlab platform.
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THE JOURNAL Or PHARYACOLOCY AND EXPERIMENTAL n(ERAPEUTIC8 Adenosine Al Receptor Activation Mediates Suppression of (-)- Bicuculline Methiodide-Induced Seizures in Rat Prepiriform Cortex1
2020Co-Authors: Paul H. Franklin, Ge Zhang, E. D. Tripp, Thomas F. MurrayAbstract:ABSTRACT The protective effects of a series of stable adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide into the rat Prepiriform Cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido-adenosine (NECA), cyclohexyladenosine, cyclopentyladenosine, 2-chloroadenosine and R-and S-phenylisopropyladenosine (R-and S-PIA), protected animals against seizures in a dosedependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses r 6.8 pmol. In contrast, heroic doses of the A, selective ligand, 2-phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA > cyclohexyladenosine > cyclopentyladenosine r R-PIA > 2chloroadenosine > S-PIA 3 Bphenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A, adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA d i i s e s to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodideinduced seizures. These results suggest that adenosine A, receptors may participate in the normal inhib itory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy. The inhibitory effects of adenosine on CNS function are manifold, and a compelling body of evidence now attests to the physiological relevance of these actions. Adenosine exerts its inhibitory influence in the CNS through activation of cell surface receptors a t both pre-and postsynaptic locations, and mechanisms for its synthesis, release and high-affinity uptake have been described in the mammalian CNS Many tissues and organ systems including the CNS contain a t least two classes of membrane-associated adenosine receptors which are coupled with opposing polarities to regulation of adenylyl cyclase activity. Adenosine receptors thus have been classified as A, or A, based on their capacity to inhibit or stimulate the rate of cyclic AMP synthesis, respectively, upon activation by adenosine agonists (Hamprecht and Vancalker, 1985
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the σ receptor ligand 1 3 di 2 tolyl guanidine is anticonvulsant in the rat Prepiriform Cortex
European Journal of Pharmacology, 1993Co-Authors: Jane E Roth, Paul H. Franklin, Thomas F. MurrayAbstract:Abstract Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED 50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (−)-bicuculline methiodide in the rat Prepiriform Cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic σ ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve σ receptors.
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Manipulation of endogenous adenosine in the rat Prepiriform Cortex modulates seizure susceptibility.
The Journal of pharmacology and experimental therapeutics, 1993Co-Authors: Ge Zhang, Paul H. Franklin, Thomas F. MurrayAbstract:A1 adenosine receptors in the rat Prepiriform Cortex play an important role in the inhibition of bicuculline methiodide-induced convulsions. In the present study we evaluated manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the rat Prepiriform Cortex. Administration of exogenous adenosine afforded a dose-dependent protection (ED50 = 48.1 +/- 8.4 nmol) against bicuculline methiodide-induced seizures, and these anticonvulsant effects were significantly potentiated by treatment with an adenosine kinase inhibitor, 5'-amino-5'-deoxyadenosine; by the adenosine transport blockers, dilazep or nitrobenzylthioinosine 5'-monophosphate; and by an adenosine deaminase inhibitor, 2'-deoxycoformycin. When administered alone, 5'-amino-5'-deoxyadenosine, 5'-iodotubercidin and dilazep were found to be highly efficacious as anticonvulsants with respective ED50 values of 2.6 +/- 0.8, 4.0 +/- 2.7 and 5.6 +/- 1.5 nmol. In contrast, 2'-deoxycoformycin was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the central nervous system. The adenosine antagonist, 8-(p-sulfophenyl)theophylline, increased markedly the severity of bicuculline methiodide-induced seizures. Moreover, reduction of extracellular adenosine formation by a focal injection of an ecto-5'-nucleotidase inhibitor, alpha, beta-methyleneadenosine diphosphate, produced generalized seizures (ED50 = 37.3 +/- 22.7 nmol). Together the proconvulsant effect of an adenosine receptor antagonist and the convulsant action of an ecto-5'-nucleotidase inhibitor further support the role of endogenous adenosine as a tonically active antiepileptogenic substance in the rat Prepiriform Cortex.
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dextrorotatory opioids and phencyclidine exert anticonvulsant action in Prepiriform Cortex
European Journal of Pharmacology, 1992Co-Authors: Jane E Roth, Thomas F. Murray, Ge Zhang, Paul H. FranklinAbstract:We have investigated the ability of an array of putative noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists to suppress convulsions induced by a unilateral, focal injection of (−)-bicuculline methiodide (118 pmol) into the rat Prepiriform Cortex. The anticonvulsant potency of these compounds, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801)>dextrorphan ⩾ 1-(1-phenylcyclohexyl)piperidine hydrochloride (PCP)>dextromethorphan > (+)-pentazocine, upon microinjection into the Prepiriform Cortex, was highly correlated (r = 0.971; P < 0.01) with their respectiv affinities for the [3H]dextrorphan-labelled NMDA receptors in rat forebrain membranes. These results suggest that noncompetitive antagonism of NMDA receptors underlies the anticonvulsant action of these compounds.
Maria J Vidal - One of the best experts on this subject based on the ideXlab platform.
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l arginine potentiates excitatory amino acid induced seizures elicited in the deep Prepiriform Cortex
European Journal of Pharmacology, 1993Co-Authors: Giovanbattista De Sarro, Eugenio Donato Di Paola, Angela De Sarro, Maria J VidalAbstract:Microinjection of N-methyl-D-aspartate (NMDA; 1 and 2.5 nmol) or kainate (KA; 50 pmol) into the deep Prepiriform Cortex elicited behavioral signs of seizure activity. No epileptiform activity was observed after deep Prepiriform Cortex microinjection of either L-arginine (L-Arg, 5 and 10 nmol) or its D-enantiomer, D-arginine (D-Arg, 2.5-10 nmol). However, both the seizure score and the incidence of electroencephalographic (EEG) epileptic discharges elicited by NMDA (1 and 2.5 nmol) and KA (50 pmol) were significantly increased by L- but not D-Arg. The facilitatory effects of L-Arg on seizure activity elicited by both NMDA and KA were dose-dependent and could be prevented by co-administration of L-Arg (10 nmol) and the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 20 nmol). Motor and electrocortical seizures were observed after microinjection of the NO donor sodium nitroprusside (SNP; 5 to 20 nmol) into the deep Prepiriform Cortex. Infusion of methylene blue (20 nmol), a soluble guanylate cyclase inhibitor, protected against SNP-induced seizures. Furthermore, prior infusion of a subconvulsant dose of SNP into the deep Prepiriform Cortex significantly potentiated the seizure activity elicited by either NMDA (1 and 2.5 nmol) or KA (50 pmol). These results support the proposal that NO is formed from L-Arg upon excitatory amino acid receptor activation within the deep Prepiriform Cortex, thereby contributing to the genesis of seizure activity.
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role of nitric oxide in the genesis of excitatory amino acid induced seizures from the deep Prepiriform Cortex
Fundamental & Clinical Pharmacology, 1991Co-Authors: G B De Sarro, Angela De Sarro, Donato E Di Paola, Maria J VidalAbstract:Summary— The role of nitric oxide (NO) in the genesis of motor and electrocortical seizures elicited by administration of excitatory amino acid agonists into the deep Prepiriform Cortex (DPC) has been evaluated. Motor and electrocortical seizures occurred in rats receiving unilateral microinjections into the DPC of either N-methyl-d-aspartate (NMDA, 5 and 10 nmol) or kainate (KA, 100 pmol). The selective NMDA receptor antagonist 2-amino-7-phosphonoheptanoate (APH), when microinjected into DPC, prevented the development of seizures induced by both NMDA and KA injected in the same site. In addition, methylene blue (20 nmol, which prevents activation of soluble guanylate cyclase) or NG-monomethyl-l-arginine (NMMA, 40 nmol; a specific inhibitor of nitric oxide synthesis), when microinjected into DPC 15 min prior to either NMDA or KA, significantly protected against seizures elicited by both excitatory amino acid agonists. These data confirm the role of excitatory amino acid transmission in the genesis of seizures elicited from the deep Prepiriform Cortex. They further suggest that activation of excitatory amino acid receptors within the DPC leads to the release of a substance which shares properties with EDRF/NO and contributes to the genesis of seizure activity in this area.