Biomedical subjects

A Vezzani

Publications and source records attributed to A Vezzani.

At least 19 recordsLinked to original sources

PubMed2006

The IL-1beta system in epilepsy-associated malformations of cortical development.

Focal cortical dysplasia (FCD) and glioneuronal tumors (GNT) are recognized causes of chronic intractable epilepsy. The cellular mechanism(s) underlying their epileptogenicity remain largely unknown. Compelling evidence in experimental models of seizures indicates an important role of interleukin (IL)-1beta in the mechanisms of hyperexcitability leading to the occurrence of seizures. We immunocytochemically investigated the brain expression and cellular distribution pattern of IL-1beta, IL-1 receptor (IL-1R) types I and II and IL-1R antagonist (IL-1Ra) in FCD and GNT specimens, and we correlate these parameters with the clinical history of epilepsy in patients with medically intractable seizures. In normal control cortex, and in perilesional regions with histologically normal cortex, IL-1beta, IL-1Rs and IL-1Ra expression was undetectable. In all FCD and GNT specimens, IL-1beta and its signalling receptor IL-1RI were highly expressed by more than 30% of neurons and glia whereas the decoy receptor IL-RII and IL-Ra were expressed to a lesser extent by approximately 10% and 20% of cells, respectively. These findings show a high expression of IL-1beta and its functional receptor (IL-1RI) in FCD and GNT specimens together with a relative paucity of mechanisms (IL-1RII and IL-1Ra) apt to inactivate IL-1beta actions. Moreover, the number of IL-1beta- and IL-1RI-positive neurons was positively correlated with the frequency of seizures, whereas the number of IL-1Ra-positive neurons and astroglial cells was negatively correlated with the duration of epilepsy prior to surgery. The expression of IL-1beta family members in these developmental lesions may contribute to their intrinsic and high epileptogenicity, thus possibly representing a novel target for antiepileptic strategies.

Adolescent↗

PubMed2006

Topological filters and high-pass/low-pass devices for solitons in inhomogeneous networks.

We show that, by inserting suitable finite networks at a site of a chain, it is possible to realize filters and high-pass/low-pass devices for solitons propagating along the chain. The results are presented in the framework of coupled optical waveguides; possible applications to different contexts, such as photonic lattices and Bose-Einstein condensates in optical networks are also discussed. Our results provide a first step in the control of the soliton dynamics through the network topology.

Journal Article↗

PubMed2006

Aging dynamics and the topology of inhomogenous networks.

We study phase ordering on networks and we establish a relation between the exponent a(x) of the aging part of the integrated auto-response function and the topology of the underlying structures. We show that a(x) > 0 in full generality on networks which are above the lower critical dimension d(L), i.e., where the corresponding statistical model has a phase transition at finite temperature. For discrete symmetry models on finite ramified structures with T(c) = 0, which are at the lower critical dimension d(L), we show that a(x) is expected to vanish. We provide numerical results for the physically interesting case of the 2 - d percolation cluster at or above the percolation threshold, i.e., at or above d(L), and for other networks, showing that the value of a(x) changes according to our hypothesis. For O(N) models we find that the same picture holds in the large-N limit and that a(x) only depends on the spectral dimension of the network.

Journal Article↗

PubMed2005

Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system.

Interleukin-1beta is rapidly synthesized by glia after the induction of seizures. Recent evidence shows that endogenous IL-1beta has proconvulsant actions mediated by interleukin-1 receptor type I. This receptor also mediates interleukin-1beta effects on neuronal susceptibility to neurotoxic insults. In this study, we investigated the basal and seizure-induced expression of interleukin-1 receptor type I in rat forebrain to identify the cells targeted by interleukin-1beta during epileptic activity. Self-sustained limbic status epilepticus was induced in rats by electrical stimulation of the ventral hippocampus. Interleukin-1 receptor type I immunoreactivity was barely detectable in neurons in control brain tissue. During status epilepticus, interleukin-1 receptor type I was induced in the hippocampal neurons firstly, and several hours later in astrocytes localized in limbic and extralimbic areas. Neuronal interleukin-1 receptor type I expression in the hippocampus outlasted the duration of spontaneous electroencephalographic seizure and was not observed in degenerating neurons. Astrocytic expression occurred transiently, between six and 18 h after the induction of status epilepticus and was invariably found in regions of neuronal damage. These time-dependent, cell- and region-specific changes in interleukin-1 receptor type I expression during status epilepticus suggest that interleukin-1 receptor type I in neurons mediates interleukin-1beta-induced fast changes in hippocampal excitability while interleukin-1 receptor type I receptors in astrocytes may mediate interleukin-1beta effects on neuronal survival in hostile conditions.

Animals↗

PubMed2005

Neuropeptide Y Y5 receptors inhibit kindling acquisition in rats.

Neuropeptide Y inhibits neuronal excitability and seizures in various experimental models. This peptide delays kindling epileptogenesis but the receptors involved in this action are unknown. We have studied the role of Y5 receptors in kindling using the selective antagonist GW438014A (IC50=210 nM), a small heterocycle molecule that crosses the blood-brain barrier, and the selective peptide agonist Ala31Aib34 NPY (IC50=6.0 nM). Intraperitoneal injection of GW438014A (10 mg/kg), 30 min before the beginning of a rapid-kindling protocol, significantly accelerated the rate of kindling acquisition as compared to vehicle-injected rats. Thus, the number of electrical stimuli required to reach stages 3 and 4-5 of kindling were reduced by 50% and 25%, respectively. The average afterdischarge duration in the stimulated hippocampus was prolonged by 2-fold. Conversely, kindling rate was delayed by intracerebroventricular administration of 24 nmol Ala31Aib32 NPY. Thus, the number of stimuli necessary to reach stages 2 and 3 of kindling was increased by 3- and 4-fold, respectively. During the stimulation protocol (40 stimuli) none of the rats treated with the Y5 agonist showed stages 4-5 seizures. Twenty-four hours after the last kindling stimulation, thus during the re-test session, Y5 agonist- or antagonist-treated rats had stages 4-5 seizures as their controls. In rats treated with both the antagonist and the agonist, kindling rate was similar to vehicle-injected rats. These data indicate that Y5 receptors mediate inhibitory effects of NPY in kindling and display anticonvulsant rather then antiepileptogenic effects upon agonist stimulation.

Animals↗

PubMed2005

Altered expression of GABA(A) and GABA(B) receptor subunit mRNAs in the hippocampus after kindling and electrically induced status epilepticus.

Epilepsy may result from altered transmission of the principal inhibitory transmitter GABA in the brain. Using in situ hybridization in two animal models of epileptogenesis, we investigated changes in the expression of nine major GABA(A) receptor subunits (alpha1, alpha2, alpha4, alpha5, beta1-beta3, gamma2 and delta) and of the GABA(B) receptor species GABA(B)R1a, GABA(B)R1b and GABA(B)R2 in 1) hippocampal kindling and 2) epilepsy following electrically-induced status epilepticus (SE). Hippocampal kindling triggers a decrease in seizure threshold without producing spontaneous seizures and hippocampal damage, whereas the SE model is characterized by spontaneous seizures and hippocampal damage. Changes in the expression of GABA(A) and GABA(B) receptor mRNAs were observed in both models, and compared with those seen in other models and in human temporal lobe epilepsy. The most prominent changes were a relatively fast (24 h after kindling and electrically-induced SE) and lasting (7 and 30 days after termination of kindling and SE, respectively) reduction of GABA(A) receptor subunit delta mRNA levels (by 43-78%) in dentate granule cells, accompanied by increases in mRNA levels of all three beta-subunits (by 8-79%) and subunit gamma2 (by 11-43%). Levels of the minor subunit alpha4 were increased by up to 60% in dentate granule cells in both animal models, whereas those of subunit alpha5 were decreased 24 h and 30 days after SE, but not after kindling. In cornu ammonis 3 pyramidal cells, downregulation of subunits alpha2, alpha4, alpha5, and beta1-3 was observed in the ventral hippocampus and of alpha2, alpha5, beta3 and gamma2 in its dorsal extension 24 h after SE. Similar but less pronounced changes were seen in sector cornu ammonis 1. Persistent decreases in subunit alpha2, alpha4 and beta2 transcript levels were presumably related to SE-induced cell loss. GABA(B) receptor expression was characterized by increases in GABA(B)R2 mRNA levels at all intervals after kindling and SE. The observed changes suggest substantial and cell specific rearrangement of GABA receptors. Lasting downregulation of subunits delta and alpha5 in granule cells and transient decreases in subunit alpha2 and beta1-3 mRNA levels in cornu ammonis 3 pyramidal cells are suggestive of impaired GABA(A) receptor-mediated inhibition. Persistent upregulation of subunits beta1-3 and gamma2 of the GABA(A) receptor and of GABA(B)R2 mRNA in granule cells, however, may result in activation of compensatory anticonvulsant mechanisms.

Animals↗

PubMed2005

Propagation of discrete solitons in inhomogeneous networks.

In many physical applications solitons propagate on supports whose topological properties may induce new and interesting effects. In this paper, we investigate the propagation of solitons on chains with a topological inhomogeneity generated by inserting a finite discrete network on a chain. For networks connected by a link to a single site of the chain, we derive a general criterion yielding the momenta for perfect reflection and transmission of traveling solitons and we discuss solitonic motion on chains with topological inhomogeneities.

Journal Article↗

PubMed2003

Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases.

Interleukin (IL)-1beta is a proinflammatory cytokine implicated in various pathophysiological conditions of the CNS involving NMDA receptor activation. Circumstantial evidence suggests that IL-1beta and NMDA receptors can functionally interact. Using primary cultures of rat hippocampal neurons, we investigated whether IL-1beta affects NMDA receptor function(s) by studying (1) NMDA receptor-induced [Ca2+]i increase and (2) NMDA-mediated neurotoxicity. IL1beta (0.01-0.1 ng/ml) dose-dependently enhances NMDA-induced [Ca2+]i increases with a maximal effect of approximately 45%. This effect occurred only when neurons were pretreated with IL-1beta, whereas it was absent if IL-1beta and NMDA were applied simultaneously, and it was abolished by IL-1 receptor antagonist (50 ng/ml). Facilitation of NMDA-induced [Ca2+]i increase by IL-1beta was prevented by both lavendustin (LAV) A (500 nm) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) (1 microm), suggesting an involvement of tyrosine kinases. Increased tyrosine phosphorylation of NMDA receptor subunits 2A and 2B and coimmunoprecipitation of activated Src tyrosine kinase with these subunits was observed after exposure of hippocampal neurons to 0.05 ng/ml IL-1beta. Finally, 0.05 ng/ml IL-1beta increased by approximately 30% neuronal cell death induced by NMDA, and this effect was blocked by both lavendustin A and PP2. These data suggest that IL-1beta increases NMDA receptor function through activation of tyrosine kinases and subsequent NR2A/B subunit phosphorylation. These effects may contribute to glutamate-mediated neurodegeneration.

Animals↗

PubMed2002

Diffusive thermal dynamics for the Ising ferromagnet.

We introduce a thermal dynamics for the Ising ferromagnet where the energy variations occurring within the system exhibit a diffusive character typical of thermalizing agents such as, e.g., localized excitations. Time evolution is provided by a walker hopping across the sites of the underlying lattice according to local probabilities depending on the usual Boltzmann weight at a given temperature. Despite the canonical hopping probabilities the walker drives the system to a stationary state which is not reducible to the canonical equilibrium state in a trivial way. The system still exhibits a magnetic phase transition occurring at a finite value of the temperature larger than the canonical one. The dependence of the model on the density of walkers realizing the dynamics is also discussed. Interestingly the differences between the stationary state and the Boltzmann equilibrium state decrease with increasing number of walkers.

Journal Article↗

PubMed2002

Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y.

Functional studies in epileptic tissue indicate that neuropeptide Y and some of its peptide analogs potently inhibit seizure activity. We investigated seizure susceptibility in transgenic rats overexpressing the rat neuropeptide Y gene under the control of its natural promoter. Seizures were induced in adult transgenic male rats and their wild-type littermates by i.c.v. injection of 0.3 microg kainic acid or by electrical kindling of the dorsal hippocampus. Transgenic rats showed a significant reduction in the number and duration of electroencephalographic seizures induced by kainate by 30% and 55% respectively (P<0.05 and 0.01). Transgenic rats were also less susceptible to epileptogenesis than wild-type littermates as demonstrated by a 65% increase in the number of electrical stimuli required to induce stage 5 seizures (P<0.01). This phenotype was associated with a strong and specific expression of neuropeptide Y mRNA in area CA1, a brain area involved in the seizure network. We conclude that endogenous neuropeptide Y overexpression in the rat hippocampus is associated with inhibition of seizures and epileptogenesis suggesting that this system may be a valuable target for developing novel antiepileptic treatments.

Animals↗

PubMed2002

Somatostatin receptor subtypes 2 and 4 affect seizure susceptibility and hippocampal excitatory neurotransmission in mice.

We have investigated the role of somatostatin receptor subtypes sst2 and sst4 in limbic seizures and glutamate-mediated neurotransmission in mouse hippocampus. As compared to wild-type littermates, homozygous mice lacking sst2 receptors showed a 52% reduction in EEG ictal activity induced by intrahippocampal injection of 30 ng kainic acid (P < 0.05). The number of behavioural tonic-clonic seizures was reduced by 50% (P < 0.01) and the time to onset of seizures was doubled on average (P < 0.05). Seizure-associated neurodegeneration was found in the injected hippocampus (CA1, CA3 and hilar interneurons) and sporadically in the ipsilateral latero-dorsal thalamus. This occurred to a similar extent in wild-type and sst2 knock-out mice. Intrahippocampal injection of three selective sst2 receptor agonists in wild-type mice (Octreotide, BIM 23120 and L-779976, 1.5-6.0 nmol) did not affect kainate seizures while the same compounds significantly reduced seizures in rats. L-803087 (5 nmol), a selective sst4 receptor agonist, doubled seizure activity in wild-type mice on average. Interestingly, this effect was blocked by 3 nmol octreotide. It was determined, in both radioligand binding and cAMP accumulation, that octreotide had no direct agonist or antagonist action at mouse sst4 receptors expressed in CCl39 cells, up to micromolar concentrations. In hippocampal slices from wild-type mice, octreotide (2 micro m) did not modify AMPA-mediated synaptic responses while facilitation occurred with L-803087 (2 micro m). Similarly to what was observed in seizures, the effect of L-803087 was reduced by octreotide. In hippocampal slices from sst2 knock-out mice, both octreotide and L-803087 were ineffective on synaptic responses. Our findings show that, unlike in rats, sst2 receptors in mice do not mediate anticonvulsant effects. Moreover, stimulation of sst4 receptors in the hippocampus of wild-type mice induced excitatory effects which appeared to depend on the presence of sst2 subtypes, suggesting these receptors are functionally coupled.

Animals↗

PubMed2001

Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration.

Pentraxin 3, a prototypic long pentraxin, is induced by proinflammatory signals in the brain. Inflammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, specific neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 -/- mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.

2-Amino-5-phosphonovalerate↗

PubMed2000

Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice.

IL-1beta and its endogenous receptor antagonist (IL-1Ra) are rapidly induced by seizures in the rodent hippocampus. Exogenously applied IL-1beta prolongs seizures in an IL-1R type I-mediated manner. This effect depends on N-methyl-d-aspartate receptor activation. We report here that intrahippocampal application of recombinant IL-1Ra or its selective endogenous overexpression in astrocytes under the control of glial acidic fibrillary protein promoter potently inhibits motor and electroencephalographic seizures induced by bicuculline methiodide in mice. Accordingly, transgenic mice show a reduced seizure-related c-fos mRNA expression in various forebrain areas compared with their wild-type littermates. Recombinant IL-1Ra was ineffective in mice deficient in IL-1R type I, having per se a delayed onset to generalized convulsions. These results demonstrate that IL-1Ra mediates potent anticonvulsant effects acting on IL-1R type I and suggest that the balance between brain IL-1beta and IL-1Ra represents a crucial mechanism to control seizure generalization.

Animals↗

PubMed2000

Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus.

Limbic status epilepticus was induced in rats by unilateral 60-min electrical stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1beta (445%), interleukin-6 (405%) and tumour necrosis factor-alpha (264%) and at 24 h for interleukin-1 receptor antagonist (494%) and inducible nitric oxide synthase (432%). In rats with spontaneous seizures (60 days after status epilepticus), interleukin-1beta mRNA was still higher than controls (241%). Immunocytochemical staining of interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha was enhanced in glia with a time-course similar to that of the respective transcripts. Sixty days after status epilepticus, interleukin-1beta immunoreactivity was increased exclusively in neurons in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 microg/3 microL) significantly decreased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-alpha content in the hippocampus measured 18 h after status epilepticus. Thus, the induction of spontaneously recurring seizures in rats involves the activation of inflammatory cytokines and related pro- and anti-inflammatory genes in the hippocampus. These changes may play an active role in hyperexcitability of the epileptic tissue.

Animals↗

PubMed2000

Modulatory role of neuropeptides in seizures induced in rats by stimulation of glutamate receptors.

Stimulation of glutamate receptors has been reported to modulate the expression of neuropeptides and their receptors in neurons. On the other hand, neuropeptides are known to regulate the presynaptic glutamate release and neuronal responses to excitatory neurotransmission. This evidence indicates a functional interaction between glutamatergic and neuropeptidergic transmission in the central nervous system (CNS). In this report, we provide pharmacologic evidence in experimental models of seizures, suggesting that somatostatin (SRIF) and neuropeptide Y (NPY) are endogenous modulators of glutamate-mediated hyperexcitability in the CNS. Electroencephalographic (EEG) and behavioral seizures were induced in rats by intrahippocampal or systemic injection of kainic acid, a glutamate analog. The number of EEG seizures and their total duration were inhibited significantly by intracerebral application of a SRIF(1) receptor agonist. Similarly, kainate seizures were reduced by N[-2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl-D-arginamide++ +] (BIBP 3226), a NPY Y(1) receptor antagonist. Enhanced seizure susceptibility to pentylentetrazol, ensuing in rats after a systemic administration of kainic acid, was reduced significantly by intracerebral application of RC 160, a SRIF(1) receptor agonist, or NPY 13-36, a Y(2)/Y(5) receptor agonist. This evidence suggests that neuropeptide analogs may be of value for controlling seizures and possibly in other pathologic conditions associated with excessive glutamate function.

Animals↗

PubMed2000

Plastic changes in neuropeptide Y receptor subtypes in experimental models of limbic seizures.

PURPOSE: Neuropetide Y (NPY)-mediated neurotransmission in the hippocampus is altered by limbic seizures. The functional consequences of this change are still unresolved and clearly depend on the type of NPY receptors involved. NPY Y2 and Y1 receptors are increased on mossy fiber terminals and decreased on granule cell dendrites after seizures, respectively. We investigated (a) whether seizures modify the NPY Y5 receptors in the hippocampus, and (b) the effect of an agonist at Y2/Y5 receptors and antagonists at Y1 receptors on acute and chronic seizure susceptibility. METHODS: Limbic seizures were induced in rats by electrical stimulation of the dorsal hippocampus, leading to stage 5 kindled seizures, or by intrahippocampal or systemic injections of kainic acid. Pentylentetrazol was administered to epileptic rats to assess their enhanced susceptibility to seizures. NPY Y5 receptor protein was measured in hippocampal homogenates using a specific polyclonal antibody and quantitative Western blotting. RESULTS: Y5 receptors (57-kD band) were transiently decreased (23 to 35%) in all hippocampal subregions 2 and 7 days, but not 2.5 hours, after seizures induced by systemic kainic acid. A minor band of 51 kD was reduced significantly in CA3 and dentate gyrus, although it was increased in CA1, 30 days after seizures, suggesting long-term posttranslational changes in this protein. NPY Y5 receptors were increased by 200% in total homogenate from the stimulated hippocampus 2 days but not 30 days after fully kindled seizures. Intracerebral injections of NPY 13-36 (Y2/Y5 receptor agonist) or BIBP 3225 and BIBO 3304 (selective Y1 receptor antagonists) decreased seizure susceptibility in rats. CONCLUSIONS: These results indicate that NPY Y5 receptors change after limbic seizures and suggest that NPY receptors may provide novel target(s) for the treatment of epilepsy.

Animals↗

PubMed1999

Interleukin-1beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures.

Using immunocytochemistry and ELISA, we investigated the production of interleukin (IL)-1beta in the rat hippocampus after focal application of kainic acid inducing electroencephalographic (EEG) seizures and CA3 neuronal cell loss. Next, we studied whether EEG seizures per se induced IL-1beta and microglia changes in the hippocampus using bicuculline as a nonexcitotoxic convulsant agent. Finally, to address the functional role of this cytokine, we measured the effect of human recombinant (hr)IL-1beta on seizure activity as one marker of the response to kainate. Three and 24 hr after unilateral intrahippocampal application of 0.19 nmol of kainate, IL-1beta immunoreactivity was enhanced in glia in the injected and the contralateral hippocampi. At 24 hr, IL-1beta concentration increased by 16-fold (p < 0.01) in the injected hippocampus. Reactive microglia was enhanced with a pattern similar to IL-1beta immunoreactivity. Intrahippocampal application of 0.77 nmol of bicuculline methiodide, which induces EEG seizures but not cell loss, enhanced IL-1beta immunoreactivity and microglia, although to a less extent and for a shorter time compared with kainate. One nanogram of (hr)IL-1beta intrahippocampally injected 10 min before kainate enhanced by 226% the time spent in seizures (p < 0.01). This effect was blocked by coinjection of 1 microgram (hr)IL-1beta receptor antagonist or 0.1 ng of 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate, selective antagonists of IL-1beta and NMDA receptors, respectively. Thus, convulsant and/or excitotoxic stimuli increase the production of IL-1beta in microglia-like cells in the hippocampus. In addition, exogenous application of IL-1beta prolongs kainate-induced hippocampal EEG seizures by enhancing glutamatergic neurotransmission.

Animals↗

PubMed1999

Neuropeptide Y: emerging evidence for a functional role in seizure modulation.

The high concentration of the tyrosine-rich polypeptide, neuropeptide Y (NPY), and the increase in the number of its receptor subtypes that have been characterized in the brain, raise the question of a functional role for NPY in the CNS. In addition to its peripheral actions on cardiovascular regulation, much attention has, therefore, been devoted to the CNS effects of NPY because of its stimulatory properties on food intake, its role in anxiolysis and its putative involvement in memory retention. Emerging evidence points to an important role for NPY in the regulation of neuronal activity both under physiological conditions and during pathological hyperactivity such as that which occurs during seizures. This article reviews recent studies that have shown the changes induced by seizures in the level and distribution of NPY, its receptor subtypes and their respective mRNAs in rat forebrain. Biochemical and electrophysiological findings in experimental models and tissue from human epilepsy sufferers suggest that NPY-mediated neurotransmission is altered by seizures. The pharmacological evidence and functional studies in NPY knockout mice highlight a crucial role for endogenous NPY, acting on different NPY receptors, in the control of seizures.

Animals↗