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Introduction
I am interested in nonlinear analysis of epileptic EEGs, using recurrence analysis as well as fractal analysis.
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Publications (55)
Objective
Variability in the frequency, timing, and pattern of seizures may influence the assessment of the effect of antiseizure medications (ASMs) when measuring seizure frequency, especially in patients with infrequent seizures. A low seizure rate is an exclusion criterion for enrollment of patients with epilepsy in clinical trials and requires...
Objective
Physical exercise may improve neurological deficits and neuronal damage after acute brain injuries and decrease established seizures. We investigated whether voluntary running wheel (RW) activity affects epileptogenesis in a mouse model of acquired epilepsy compared to sedentary mice.
Methods
Epilepsy was induced by intra‐amygdala kainat...
The latency between traumatic brain injury (TBI) and the onset of epilepsy (PTE) represents an opportunity for counteracting epileptogenesis. Antiepileptogenesis trials are hampered by the lack of sensitive biomarkers that allow to enrich patient's population at-risk for PTE. We aimed to assess whether specific ECoG signals predict PTE in a clinica...
Therapies for epilepsy mainly provide symptomatic control of seizures since most of the available drugs do not target disease mechanisms. Moreover, about one-third of patients fail to achieve seizure control. To address the clinical need for disease-modifying therapies, research should focus on targets which permit interventions finely balanced bet...
Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease-preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs...
The lack of early biomarkers of epileptogenesis precludes a sound prediction of epilepsy development after acute brain injuries and of the natural course of the disease thus impairing the development of antiepileptogenic treatments. We investigated whether the dimensional changes of nonlinear dynamics in EEG/ECoG signals, that were recorded in the...
Objective
Status epilepticus (SE) is a life‐threatening and commonly drug‐refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) and a major contributor to t...
Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease-preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs...
Postinjury epilepsy (PIE) is a devastating sequela of various brain insults. While recent studies offer novel insights into the mechanisms underlying epileptogenesis and discover potential preventive treatments, the lack of PIE biomarkers hinders the clinical implementation of such treatments. Here we explored the biomarker potential of different e...
Scientific Reports 6 : Article number: 31129 10.1038/srep31129 ; published online: 04 August 2016 ; updated: 14 October 2016 The Acknowledgements section in this Article is incorrect.
The lack of a marker of epileptogenesis is an unmet medical need, not only from the clinical perspective but also from the point of view of the pre-clinical research. Indeed, the lack of this kind of marker affects the investigations on the mechanisms of epileptogenesis as well as the development of novel therapeutic approaches aimed to prevent or...
Pre-clinical studies aimed to test potential anti-epileptogenic therapies by using the animal models of epileptogenesis induced by status epilepticus (SE), highlighted that the early days following the end of this primary insult represent a crucial temporal window for the subsequent development of epilepsy. In this study, we characterized the EEG d...
The pathophysiology of cerebral cortical lesions in multiple sclerosis (MS) is not understood. We investigated cerebral cortex microvessels during immune-mediated demyelination in the MS model chronic murine experimental autoimmune encephalomyelitis (EAE) by immunolocalization of the endothelial cell tight junction (TJ) integral proteins claudin-5...
Nowadays, a hot topic in the field of epilepsy research is the detection of any reliable marker, embedded in the electroencephalograms (EEGs), that can be exploited to predict the seizure with a sufficient advance notice. A useful analytical tool which may help epileptologists to unveil significant patterns in EEGs of people suffering from epilepsy...
Temporal lobe epilepsy remains amongst the most common and drug refractory of neurological disorders. Gene therapy may provide a realistic therapeutic approach alternative to surgery for intractable focal epilepsies. To test this hypothesis, we applied here a gene therapy approach, using a recombinant adeno-associated viral (rAAV) vector expressing...
We examined the blood-brain barrier (BBB) function in methylazoxymethanol acetate (MAM)-treated rats, a model of human developmental brain malformations. We found aberrant vessels morphology and serum albumin leakage in the heterotopic (malformed) hippocampus; these changes were associated with a significant increase in endothelial P-glycoprotein (...
Erythropoietin (EPO) mediates a wide range of neuroprotective activities, including amelioration of disease and neuroinflammation in rat models of EAE. However, optimum dosing parameters are currently unknown. In the present study, we used a chronic EAE model induced in mice by immunization with the myelin oligodendrocyte glycoprotein peptide (MOG3...
Purpose:
We measured the brain-to-plasma partition of 10,11-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide (10-OHCBZ) in epilepsy patients undergoing surgery to alleviate drug-resistant seizures and administered with different oral doses of oxcarbazepine (OXC). We addressed the possible contribution of the multidrug transporter P-glycopro...
We investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid-induced status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats.
Limbic seizures were induced by systemic injection of kainic acid. Glia activation and neuronal cell loss were studied by using im...
There is recent evidence that increased expression of multidrug transporters, such as P-glycoprotein (P-gp), may lead to reduced antiepileptic drug (AED) concentrations in the brain, shortly after status epilepticus (SE), thereby suggesting a possible mechanism for drug-resistance. To get insights on whether increased P-gp expression is a consequen...
In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal inj...
The causes and mechanisms underlying multidrug resistance (MDR) in epilepsy are still elusive and may depend on inadequate drug concentration in crucial brain areas. We studied whether limbic seizures or anticonvulsant drug treatments in rodents enhance the brain expression of the MDR gene (mdr) encoding a permeability glycoprotein (P-gp) involved...
Glutamate-induced excitotoxicity is suggested to play a central role in the development of amyotrophic lateral sclerosis (ALS), although it is still unclear whether it represents a primary cause in the cascade leading to motor neurone death. We used western blotting, immunocytochemistry and in situ hybridization to examine the expression of GLT-1 i...
Glutamate-induced excitotoxicity is suggested to play a central role in the development of amyotrophic lateral sclerosis (ALS), although it is still unclear whether it represents a primary cause in the cascade leading to motor neurone death. We used western blotting, immunocytochemistry and in situ hybridization to examine the expression of GLT-1 i...
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 n...
We studied ionotropic glutamate receptor subtypes and the effect of chronic treatment with NBQX [6-nitro-7-sulphamoyl-benzo(F)quinoxaline-2,3-dione], a selective ( rs)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, in the spinal cord of mnd mice. NBQX (8 mg/kg daily i.p. for 3 weeks starting from 24 weeks old) sig...
Seizures increase the synthesis of brain-derived neurotrophic factor in forebrain areas, suggesting this neurotrophin has biological actions in epileptic tissue. The understanding of these actions requires information on the sites and extent of brain-derived neurotrophic factor production in areas involved in seizures onset and their spread. In thi...
The presence and distribution within the CNS of various peptides and their receptors, many of which were originally characterized in non-neural tissues, have raised many questions regarding their function and mechanisms of action. Many neuroactive peptides are often co-localized in neurons with classical neurotransmitters (i.e. biogenic amines or a...
The suggestion that somatostatin is involved in the pathophysiology of obsessive-compulsive disorder and the evidence that selective serotonin reuptake inhibitors show significant antiobsessional effect prompted us to examine the effect of citalopram, a selective and potent serotonin reuptake inhibitor, on the somatostatinergic system in different...
Recent studies have demonstrated that neuropeptide expression in forebrain neurons is responsive to changes in physiological activity. This is particularly true in the hippocampus where the expression of various neuropeptides has been reported to change in distinct neuronal populations in response to seizure activity. The aim of this work is to rev...
In situ hybridization histochemistry for somatostatin receptors-1, -2, -3 and -4 section and receptor autoradiography using [125I]CGP 23996, [125I]somatostatin-28, [125I]seglitide and [125I]Tyr3 octreotide were carried out to determine the expression of somatostatin receptor messenger RNAs and binding sites in the hippocampus and cerebral cortex of...
Chronic treatment of adult rats with DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic carboxyethylester (CGP 39551) (30 mg/kg orally for 12 days) induced a significant increase, 72 h after the last dose, in the N-methyl-D-aspartate (NMDA)-sensitive [3H]glutamate binding in the hippocampal pyramidal layer (stratum oriens CA1, CA3: +51% on average; st...
We measured the release of neuropeptide Y (NPY) from hippocampal slices of rats at various times after limbic seizures induced by a subcutaneous injection of 12 mg/kg kainic acid (KA). Two days after KA, 100 mM KCl induced a 1.6 +/- 0.2-fold increase in NPY release compared to saline-injected rats (P < 0.05), while spontaneous and 50 mM KCl-induced...
The N-methyl-D-aspartate (NMDA) receptors are a class of excitatory amino acid receptors in the brain which are important for the induction of kindling and kindling-like phenomena. Post hoc sodium nitroprusside-induced ADP ribosylation of some proteins (particularly a p43 and a p39 protein) in homogenates from stimulated hippocampus was reduced at...
The release of neuropeptide Y (NPY) was measured from hippocampal slices of rats at stage 2 (preconvulsive stage) and stage 5 (full seizure expression) of electrical kindling of the dorsal hippocampus (upper blade of the dentate gyrus). Spontaneous release in naive rats (9.0 +/- 0.8 fmol/ml every 10 min) was independent of external Ca2+ but was red...
Intracerebral microdialysis combined with a sensitive and specific radioimmunoassay was used to monitor the neuronal release of somatostatin (somatostatin-like immunoreactivity, SLI) in the dorsal hippocampus of freely moving rats. The sensitivity of the radioimmunoassay was optimized to detect < 1 fmol/ml. The basal concentration of SLI in 20-min...
A somatostatin-specific antibody (Ab) (1:250) was continuously infused into the stimulated dorsal hippocampus of rats from 4 days before to 26 days after the beginning of kindling or until the first stage 5. Controls received boiled Ab. The number of stimulations to the first stage 5 were reduced by 41 +/- 4% (P < 0.01, Student's t-test) in animals...
The release of somatostatin (somatostatin-like immunoreactivity) from hippocampal slices during the development of hippocampal kindling in rats was measured under resting and depolarizing conditions. Preliminary experiments in naive rats showed that the spontaneous efflux of somatostatin (4.0 +/- 0.3 fmol/ml every 10 min) was independent of externa...
The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10 nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells. We examined the effects of these infusions on discrete cellular populations. The distribution of somatostatin (SOM)-positive neurons labelled by immunocytochemistry or by NADPH-diaphorase...
We investigated whether in vivo excitotoxicity was mediated by a mechanism of programmed cell death called apoptosis. Neurotoxic doses of kainic acid (1.2 nmol) and quinolinic acid (120 nmol) were unilaterally injected in the dorsal hippocampus of anesthetized rats. Eight or 16 h later the animals were killed and DNA was extracted from the injected...
In this study we examined whether the potency of quinolinic acid (Quin) in inducing neurodegeneration in vivo was dependent on the exposure time of the tissue to the excitotoxin. The effect of chronic infusion of Quin into rat striatum and hippocampus was examined at the light microscopic level and by cell count on 40 microm Cresyl violet stained b...
We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates [( 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulat...
Electroencephalographic (EEG) seizures were measured in rats after intrahippocampal injection of 120 nmol quinolinic acid into the stratum radiatum CA1 or 0.19 nmol kainic acid in the dentate gyrus or in the stratum radiatum. Injection of 5 micrograms SMS 201-995, a peptidase-resistant cyclic octapeptide analogue of somatostatin, into the stratum r...
