N-valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug.

A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D pH7.4 (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments indicate high stability of c…

Effetti dell’influenza dell’ ossido nitrico su modelli di ipereccitabilità sperimentalmente indotta: studio elettrofisiologico comparativo in vivo e in vitro nel ratto.

Levetiracetam anticonvulsant activity is modulated by nitric oxide-active drugs in a model of partial complex epilepsy in the rat

Role of CB2 receptors and cGMP pathway on the cannabinoid-dependent antiepileptic effects in an in vivo model of partial epilepsy.

This study aimed at providing an insight on the possible role of cannabi-noid (CB) type 2 receptors (CB2R) and cGMP pathway in the antiepileptic activity ofWIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone, a non-selective CB agonist, in the maximal dentate activation (MDA) model of partial epilepsy in adult male rats. We evaluated the activity of a CB2 antagonist/inverse agonist AM630, [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone or 6-iodopravadoline, alone or in co-administration with WIN 55,212-2. Also, in the MDA model it was investigated the co-treatment of WIN55,212…

Effects of nitric oxide and GABA system in a rat model of temporal lobe epilepsy

NANC inhibitory innervation in rat gastric fundus:role of cannabinoids

Cannabinoid-‐mediated modulation of hippocampal hyperexcitability: focus on the interplay with nitrergic system in different rat models of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of partial complex seizure in adulthood [1]. Within the framework of hyperexcitability, growing interest has risen on the impact of cannabinoids on the control of paroxysmal phenomena [2], despite their reputation as psychotropic substances with addictive properties [3; 4]. In this regard, it was reported that the on-demand production of endocannabinoids from over-activated postsynaptic cells inhibits neurotransmitter release, hence protecting against excitotoxicity in the hippocampus [5; 6]. Nonetheless, the potential anticonvulsant action of cannabinoids has not been fully addressed. Indeed, CB-mediated effects in animal models are attr…

Nitric oxide influence on hippocampal hyperexcitability: in vivo and in vitro comparative electrophysiological study in the rat

Being in the Past and Perform the Future in a Virtual World: VR Applications to Assess and Enhance Episodic and Prospective Memory in Normal and Pathological Aging

The process of aging commonly features a gradual deterioration in cognitive performance and, in particular, the decline of memory. Despite the increased longevity of the world's population, the prevalence of neurodegenerative conditions, such as dementia, continues to be a major burden on public health, and consequently, the latest research has been focused on memory and aging. Currently, the failure of episodic and Prospective memory (PM) is one of the main complaints in the elderly, considered among the early symptoms of dementia. It is therefore increasingly important to define more clearly the boundaries between normal and pathological aging. Recently, researchers have begun to build an…

Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on control of hippocampal hyperexcitability

Cannabinoids (CB), transient receptors potential vanilloid type 1 (TRPV1) and nitric oxide (NO) were found to be interlinked in regulating some neuronal functions such as membrane excitability and synaptic transmission. TRPV1 play a fundamental role since it represents a synaptic target for CB that triggers several downstream cellular pathways. In this regard, recent evidence report that TRPV1 could influence NO production by modulating neuronal NO synthase (nNOS) activity. In the present research, we pointed to manipulate nNOS function to assess its role on TRPV1 signalling in hyperexcitability conditions elicited in the dentate gyrus of hippocampal formation. The activation of TRPV1 recep…

Modulation of in vivo GABA-evoked responses by nitric oxide-active compounds in the globus pallidus of rat.

Nitric oxide (NO) is a gaseous molecule acting as a messenger in both the peripheral and the central nervous systems. NO affects synaptic activity by modulating neurotransmitter release and/or receptor function. We previously observed that NO-active compounds modify the bioelectric activity of basal ganglia (BG) units. In this study, we applied microiontophoresis to extracellular in vivo recordings to investigate the effect of NO-active compounds on GABA-evoked responses in the globus pallidus (GP) of anesthetized rats. The changes induced by NO-active drugs on the GABA-induced inhibition were used as indicators of NO modulation. The response to GABA release was tested on recorded GP neuron…

Nitric oxide control of experimental model of partial epileptic seizures: in vivo and in vitro electrophysiological study in the rat.

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

Abstract Aim The effects of local applied NO-active compounds on glutamate (GLU)-evoked responses were investigated in globus pallidus (GP) neurons. Main methods Extracellularly recorded single units from anesthetized rats were treated with GLU before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro- l -arginine methyl ester (L-NAME), a NOS inhibitor. Key findings Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their excitatory responses to the administration of iontophoretic GLU. In these cell…

The discharge of subthalamic neurons is modulated by nitric oxide: a microiontophoretic study in the rat

Cannabinoids, TRPV and nitric oxide: the three ring circus of neuronal excitability

Endocannabinoid system is considered a relevant player in the regulation of neuronal excitability, since it contributes to maintaining the balance of the synaptic ionic milieu. Perturbations to bioelectric conductances have been implicated in the pathophysiological processes leading to hyperexcitability and epileptic seizures. Cannabinoid influence on neurosignalling is exerted on classic receptor-mediated mechanisms or on further molecular targets. Among these, transient receptor potential vanilloid (TRPV) are ionic channels modulated by cannabinoids that are involved in the transduction of a plethora of stimuli and trigger fundamental downstream pathways in the post-synaptic site. In this…

Nitric oxide- and cGMP-active compounds affect the discharge of substantia nigra pars reticulata neurons: in vivo evidences in the rat

The nitric oxide (NO)-active drugs influence on the bioelectric activity of neurons of the pars reticulata of the substantia nigra was studied in urethane-anesthetized rats. A first group of animals was treated with 7-nitro-indazole (7-NI), a preferential inhibitor of neuronal NO synthase. In a second group of rats, electrophysiological recordings were coupled with microiontophoretic administration of Nomega-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1, a NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission). 7-NI and L-NAME caused a statistically significant decrease in …

Nitric oxide-active compounds modulate glutamatergic and GABAergic transmission in globus pallidus of rat

The globus pallidus (GP) of rodents, homologous to the external globus pallidus of primates, plays a critical role in the expression of basal ganglia (BG) function. Glutamatergic and GABAergic inputs have been demonstrated to greatly modulate the spontaneous GP activity. In this study the effects of local applied NO-active compounds on glutamate (GLU)- and GABA-evoked responses were investigated in rat GP neurons. Extracellularly recorded single units from anesthetized rats were treated with GLU or GABA before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Most GP cells were excited by…

Nitric oxide/cGMP and lamotrigine/vigabatrin in a rat model of temporal lobe epilepsy

Antiepileptic effect of dimethyl sulfoxide in a rat model of temporal lobe epilepsy.

Dimethyl sulfoxide (DMSO) is an amphipathic molecule widely used to solubilize water-insoluble compounds. In many studies it was reported that DMSO is capable of affecting several biological processes, thus resulting in a potential cause for the misinterpretation of experimental data. Recent papers showed that DMSO modified the brain bioelectric activity in animal models of epilepsy. In an in vivo model of temporal lobe epilepsy in the rat, we examined the effects of different doses (10%, 50% and 100%) of DMSO on the maximal dentate activation (MDA). The results show that DMSO induced a dose-dependent significant reduction of the electrically induced paroxysmal activity.

Microtubule Dynamics and Neuronal Excitability: Advances on Cytoskeletal Components Implicated in Epileptic Phenomena

AbstractExtensive researches have deepened knowledge on the role of synaptic components in epileptogenesis, but limited attention has been devoted to the potential implication of the cytoskeleton. The study of the development of epilepsy and hyperexcitability states involves molecular, synaptic, and structural alterations of neuronal bioelectric activity. In this paper we aim to explore the neurobiological targets involved in microtubule functioning and cytoskeletal transport, i.e. how dynamic scaffolding of microtubules can influence neuronal morphology and excitability, in order to suggest a potential role for microtubule dynamics in the processes turning a normal neuronal network in a hy…

Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy

The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our r…

Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.

The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nω-nitro-l-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue o…

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus

In this study, the effects of microiontophoretically applied NO-active compounds on glutamate(GLU)-evoked responses were investigated in globus pallidus (GP) neurons from anesthetized rats. Most GP cells were excited by S-nitrosoglutathione (SNOG), an NO donor, whereas administration of Nω-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, induced a decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant excitatory responses to the administration of iontophoretic GLU. In these cells, the changes induced by NO-active drugs in the magnitude of GLU-evoked responses were used as indicators of NO modulation. When an NO-active drug and GLU wer…

Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.

The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatme…

Comparison of effects of Valproate and the newly synthesized Valproil-L-Tryptophan on epileptiform activity in rat brain slices

Effects of nitric oxide along basal ganglia pathways: a microiontophoretic study in the rat.

Lamotrigine and vigabatrin control of maximal dentate gyrus activation in the rat: role of nitric oxide(NO)/cGMP pathway

Nitric oxide-induced modulation of neuronal discharge in the basal ganglia of the rat

Nitric oxide modulation of direct pathway in the rat basal ganglia circuit”

Involvement of nitric oxide-soluble guanylyl cyclase pathway in the control of maximal dentate gyrus activation in the rat.

Summary Nitric oxide=soluble Guanylyl cyclase (NO=sGC) pathway on the maximal dentate gyrus activation (MDA) was studied in rats. The cerebral NO levels were modified by administrating 7-Nitroindazole (7-NI), a selective inhibitor of neuronal NOS, and L-arginine, a precursor of the synthesis of NO. 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sGC pathway, was administered to study the involvement of cGMP pathway. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle; MDA parameters studied were: onset time, MDA duration and post-stimulus afterdischarge (AD) duration. 7-NI caused an increase of M…

Nitric oxide affects the discharge of substantia nigra pars reticulata neurons: microiontophoretic evidences in the rat

The role of neurosteoids sulphate in a spatial and object recognition learning task

The term “neuroactive steroid” refers to steroids that have rapid modulatory effects on ligand-gated ion channels via non-genomic mechanism. Specifically, neurosteroids can alter neuronal excitability via the cell surface interacting with specific neurotransmitter receptors. The neurosteroid pregnenolone sulphate (PREGS) has been described as negative modulator of GABAA receptor and positive modulator of NMDA receptor, affecting cognition as well as emotionality. The present study was aimed to assess the effects of the acute administration of PREGS (10 mg/Kg, s. c.) on rats cognitive functions using a novel task, the Can test. This task explores, under reinforcement, the spatial/visual cues…

The control of maximal dentate gyrus activation: role of nitric oxide alone and in combination with lamotrigine and vigabatrin

Intensity of GABA-evoked responses is modified by nitric oxide-active compounds in the subthalamic nucleus of the rat: a microiontophoretic study.

We have previously described modulatory effects of nitric oxide (NO)-active drugs on subthalamic nucleus (STN) neurons. In this study, the effects of microiontophoretically applied NO-active compounds on GABA-evoked responses were investigated in subthalamic neurons extracellularly recorded from anesthetized rats: 45 of 62 cells were excited by S-nitroso-glutathione (SNOG), an NO donor, whereas 28 of 43 neurons were inhibited by N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Nearly all neurons responding to SNOG and/or L-NAME showed significant inhibitory responses to the administration of iontophoretic GABA. In these cells, the changes induced by NO-active drugs in the magnitud…

Effects of nitric oxide and cGMP-active compounds on neuronal activity of substantia nigra pars reticulata: a rat in vivo study

Effects of nitric oxide influence on experimentally-induced hyperexcitability of the hippocampus: In vivo and in vitro comparative electrophysiological evaluation

NITRIC OXIDE-ACTIVE COMPOUNDS MODULATE IN VIVO GABA-EVOKED RESPONSES IN THE GLOBUS PALLIDUS OF RAT

Nitric oxide (NO) acts as a messenger in the central nervous system; it affects the synaptic activity by modulating neurotransmitter release and/or receptor function. We previously observed that NO-active compounds modify the bioelectric activity of basal ganglia (BG) units. In this study, we applied microiontophoresis to extracellular in vivo recordings to investigate the effect of NO-active compounds on GABA-evoked responses in the globus pallidus (GP) of rats. The response to GABA release was tested on recorded GP neurons before and during the administration of S-nitroso-glutathione (SNOG, NO donor) and/or Nω-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase (NOS…

Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat

Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters,…

In the rat maximal dentate activation model of partial complex epilepsy, the anticonvulsant activity of levetiracetam is modulated by nitric oxide-active drugs.

The effects of nitric oxide-active drugs on the anticonvulsant action of the antiepileptic drug levetiracetam in an experimental model of partial complex seizures named maximal dentate gyrus activation were studied in rats. Levetiracetam was given alone or in combination with 7-nitroindazole, a preferential inhibitor of neuronal nitric oxide synthase, or with L: -arginine, the precursor of nitric oxide synthesis. The maximal dentate activation parameters were the time of latency and the durations of maximal dentate activation and afterdischarge responses. The administration of levetiracetam showed an anticonvulsant effect that was increased when given in combination with 7-nitroindazole. Th…

Nitric oxide modulation of the direct pathway in rat basal ganglia circuit

Lamotrigine and vigabatrin control of maximal dentate gyrus activation in the rat: role of nitric oxide (NO) / cGMP pathways

Decreased response to acetylcholine during aging of Aplysia neuron R15

How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk Aplysia californica . R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old Aplysia showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane p…

Pregnenolone sulphate enhances spatial orientation and object discrimination in adult male rats: Evidence from a behavioural and electrophysiological study

Abstract Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation–acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo , after acute PREGS systemic administration in order to investigate on the neuronal activati…

Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat

A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4- morpholinylmethyl) pyrrolo[1,…

N-Valproyl-L-Phenylalanine as new potential antiepileptic drug: Synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy

Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, …

Effects of nitric oxide influence on experimentally-induced hyperexcitability of The hippocampus: in vivo and in vitro comparative electrophysiological study in the rat.

Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat

Different studies have been shown a clear anticonvulsant activity exerted by cannabinoids (CB) through the CB1 receptor activation. The purpose of this study was to evaluate, in an in vivo experimental model of temporal lobe epilepsy (maximal dentate gyrus activation - MDA) in the rat, the protective effect of (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN 55,212-2, CB agonist) alone or in combination with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist). Pre-treatment with AM251 (1 mg kg-1, 30 min interval) dramatically reduced the signif…

Lamotrigine differently modulates 7-Nitroindazole and L-Arginine influence on Rat Maximal Dentate Gyrus Activation

The effects induced on the maximal dentate gyrus activation (MDA) by administering the anticonvulsant lamotrigine (LTG), the selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) and the precursor of nitric oxide (NO) synthesis L-arginine, alone or in combination, were studied in urethane anaesthetized rats. Either 7-NI or LTG alone administration reduced the number of convulsing animals following angular bundle (AB) stimulation; their combined treatment induced a further increase of the anticonvulsant effect as also demonstrated by the decrease of MDA and afterdischarge (AD) durations in the animals still responding to AB stimulation. On the contrary, the injection o…

Inhibitory effects of N-valproyl-L-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity in rat brain slices.

N-valproyl-l-tryptophan (VPA-Tryp), new antiepileptic drug, was tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 or 2 mM) of Valproate (VPA) or VPA-Tryp. Both burst duration and interburst frequency during and after treatment were off-line compared with baseline values. For both parameters, the latency and the length of statistically significant response periods as well as the magnitude of drug-induced responses were calculated. VPA-Tryp evoked fewer and weaker early excitatory effects than VPA on …

Hippocampal hyperexcitability is modulated by microtubule-active agent: evidence from in vivo and in vitro epilepsy models in the rat

The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological epileptiform activity in the rat hippocampus. To this aim, we used in vivo Maximal Dentate Activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to asse…

Nitric oxide/cGMP and Lamotrigine/Vigabatrin effects in a rat model of temporal lobe epilepsy.

Studio del ruolo dell’ossido nitrico nella modulazione dell’attività bioelettrica del complesso strio-pallido-subtalamico del ratto