Acute Epileptic Seizures Research Articles

Microglia depletion exacerbates acute seizures and hippocampal neuronal degeneration in mouse models of epilepsy.

Epileptic seizures are the manifestation of hypersynchronous and excessive neuronal excitation. While the glutamatergic and GABAergic neurons play major roles in shaping fast neuronal excitation/inhibition homeostasis, it is well illustrated that astrocytes profoundly regulate neuronal excitation by controlling glutamate, GABA, cannabinoids, adenosine, and concentration of K+ around neurons. However, little is known about whether microglia take part in the regulation of acute neuronal excitation and ongoing epileptic behaviors. We proposed that if microglia are innately ready to respond to epileptic overexcitation, depletion of microglia might alter neuronal excitability and severity of acute epileptic seizures. We found that microglia depletion by plx3397, an inhibitor of CSF1R, exacerbates seizure severity and excitotoxicity-induced neuronal degeneration, indicating that microglia are rapidly responsive to the change of excitation/inhibition homeostasis and participate in the protection of neurons from overexcitation.

Analysis of rat blood plasma upon acute epileptic seizures by infrared spectroscopy with chemometrics

Blood monitoring provides convenient and minimally invasive method to follow-up the patients suffering from epilepsy. For such analysis, Fourier transform infrared (FT-IR) spectroscopy offers rapid, versatile and relatively non-invasive approach which could determine epilepsy induced biomolecular alterations in blood. In the present study, FT-IR spectroscopy combined with chemometrics such as principal component (PCA) and hierarchical cluster analysis (HCA) was used to analyse blood plasma from rats that experienced pentyleneterazol-induced generalized tonic-clonic seizures (GTCS). Spectral analysis was performed on second derivative spectra of plasma samples. The findings showed that when compared to control there were insignificant alterations in intensities and positions of lipid absorptions of GTCS group. However, major spectral changes such as significant increases in the intensities of α-helix (1656 cm−1 and 1547 cm-1) and β-sheet (1656 cm-1) structures in proteins were obtained. While PCA and HCA did not show a discrimination based on 3000-2800 cm-1 region (lipids), these methods successfully classified control and GTCS groups depending on 1730-1480 cm-1 (proteins), which is further supported by high specificity (85.7%) and sensitivity (100%) values. Consequently, the results suggest that FT-IR spectroscopy with multivariate analyses such as PCA and HCA may serve as a useful tool to investigate biomolecular alterations induced by acute epileptic seizures in blood plasma.

Embelin Protects Against Acute Pentylenetetrazole-Induced Seizures and Positively Modulates Cognitive Function in Adult Zebrafish.

Purpose of the research: Epilepsy is a continuous process of neurodegeneration categorized by an enduring tendency to generate uncontrolled electrical firing known as seizures causing involuntary movement all over the body. Cognitive impairment and behavioral disturbances are among the more alarming co-morbidities of epilepsy. Anti-epileptic drugs (AEDs) were found to be successful in controlling epilepsy but are reported to worsen cognitive status in patients. Embelin (EMB) is a benzoquinone derived from the plant Embelia ribes and is reported to have central nervous system (CNS) activity. This study aims to evaluate the effectiveness of EMB against pentylenetetrazole (PTZ) induced acute seizures and its associated cognitive dysfunction. This was done via docking studies as well as evaluating neurotransmitter and gene expression in the zebrafish brain. The principal results: Behavioral observations showed that EMB reduced epileptic seizures and the T-maze study revealed that EMB improved the cognitive function of the fish. The docking study of EMB showed a higher affinity toward gamma-aminobutyric acid (GABAA) receptor as compared to the standard diazepam, raising the possibility of EMB working via the alpha subunit of the GABA receptor. EMB was found to modulate several genes, neurotransmitters, and also neuronal growth, all of which play an important role in improving cognitive status after epileptic seizures. Healthy zebrafish treated with EMB alone were found to have no behavioral and biochemical interference or side effects. The immunohistochemistry data suggested that EMB also promotes neuronal protection and neuronal migration in zebrafish brains. Major Conclusions: It was perceived that EMB suppresses seizure-like behavior via GABAA receptor pathway and has a positive impact on cognitive functions. The observed effect was supported by docking study, T-maze behavior, neurotransmitter and gene expression levels, and immunohistology study. The apparatus such as the T-maze and seizure scoring behavior tank were found to be a straightforward technique to score seizure and test learning ability after acute epileptic seizures. These research findings suggest that EMB could be a promising molecule for epilepsy induced learning and memory dysfunction.

Neurological Manifestations of Sanjad–Sakati Syndrome: New Three Reported Cases from Tunisia

AbstractSanjad–Sakati syndrome (SSS), or hypoparathyroidism–mental retardation dysmorphism syndrome, is a rare autosomal recessive congenital disorder characterized by congenital hypoparathyroidism, growth and neurodevelopmental delay, acute symptomatic seizures due to hypocalcemia, and dysmorphic features. The syndrome is underdiagnosed, and neurological manifestations are not previously described. We report three Tunisian patients with SSS revealed by acute symptomatic hypocalcemic epileptic seizures. Despite the well-controlled seizures, patients tend to continue having poor growth and neurological outcome. The diagnosis of SSS allowed for proper treatment of the patients, prevented associated comorbidities, and provided genetic counseling to their families.

FORMULATION AND EVALUATION OF LORAZEPAM ENCAPSULATED COLLAGEN/PECTIN BUCCAL PATCH

Objective: To formulate and characterize Lorazepam loaded buccal patches using mucoadhesive, biodegradable, natural polymers-pectin (hydrophilic) and collagen (lipophilic) for treating epileptic seizures.
 Methods: Lorazepam loaded buccal patches were prepared by solvent casting method and were subjected to various Physico-chemical evaluation parameters to find the optimized buccal patch. The in vitro drug release study and ex vivo permeation study was carried out. The stability study and histopathological study of optimized Lorazepam loaded buccal patch was also carried out.
 Results: From in vitro drug release study, it was found that Lorazepam loaded buccal patch (B4) exhibited maximum drug release of 96.16 %±0.07 than other formulations at the end of 4 h, indicating an initial burst release followed by sustained release with release kinetics as Higuchi diffusion model. Based on the in vitro drug release, % drug content, % swelling index, folding endurance, B4 formulation was considered as optimised formulation and was further characterized. Ex vivo permeation study revealed that the cumulative amount of drug permeated from optimised Lorazepam loaded buccal patch (B4) was higher (3831.4±0.21µg/cm2) than marketed Midazolam buccal solution (1724±0.12 µg/cm2) and control drug solution (895.42±0.07 µg/cm2) with an enhancement ratio of 4.8. B4 formulation also showed a higher flux value (12.52±0.02µg/cm2/hr) compared to marketed formulation (5.732±0.01 µg/cm2) and control drug solution (2.563±0.03 µg/cm2) of P<0.05. The histopathological study using bovine buccal mucosa revealed that the B4 formulation is safe for buccal application. The stability study confirmed that B4 formulation is stable in both room and refrigeration conditions. Hence the formulated Lorazepam loaded buccal patch seems to be a promising carrier for the enhanced buccal delivery of Lorazepam in treating epileptic seizures.
 Conclusion: The formulated Lorazepam loaded collagen/pectin buccal patch was found to be an efficient and stable route for the buccal delivery of Lorazepam in treating acute epileptic seizures which could be further explored scientifically.

Lead intoxication mimicking idiopathic epilepsy in a young dog

An 11-month-old neutered female cocker spaniel was referred for two generalised tonic-clonic epileptic seizures with a one-week interval of mild depression. On admission, physical and neurological examinations were unremarkable. Neurolocalisation...

Acute epileptic seizures in myelin oligodendrocyte glycoprotein encephalomyelitis and neuromyelitis optica spectrum disorder: A comparative cohort study

BackgroundLittle is known about the incidence and characteristics of acute epileptic seizures in myelin oligodendrocyte glycoprotein encephalomyelitis (MOG-EM) and neuromyelitis optica spectrum disorder (NMOSD). In this study, we compared the incidence and characteristics of acute epileptic seizures in MOG-EM and NMOSD patients. MethodsMOG-EM (n = 61) and NMOSD (n = 565) cases obtained from the MSNMOBase (2011–2018) were retrospectively reviewed. ResultsAcute epileptic seizures were observed in 13 (21.3%) patients with MOG-EM and two (0.4%) patients with NMOSD (P < 0.001). In both MOG-EM and NMOSD patients, more than half of seizures were single and of focal onset; slow wave and cortical/subcortical lesions were the most common abnormalities. In MOG-EM patients, no difference was found in the proportion of single seizure with and without anti-epileptic drugs (AEDs; 64.3% vs. 45.5%, P = 0.435). Long-term AED use did not significantly reduce the occurrence of acute epileptic seizures, which was 66.7% before and after treatment. In patients with MOG-EM and NMOSD, mycophenolate mofetil significantly reduced acute epileptic seizure occurrence (P = 0.024). ConclusionAcute epileptic seizures were more common in MOG-EM patients than in NMOSD patients. The long-term use of AEDs might be unnecessary given the use of immunotherapy in cases of MOG-EM.

Induction of Epileptic Seizures in Mouse Models of Chronic Restraint Stress

Objective To investigate the sensitivity of mouse models of chronic restraint stress to conditions that induce epileptic seizures.Methods Male C57BL/6J mice were randomized into chronic restraint stress(CRS)group and normal control(NC)group. The modeling results were evaluated by sucrose preference test and forced swimming test. Kainic aicd(KA)was intraperitoneally injected to induce acute seizures. Seizure onset time,duration,and scores were recorded and compared.Results During the forced swimming test,the immobility time was(120.9±13.5)s in CRS group and only(59.1±9.8)s in NC group(t=3.700,P=0.0019). During the sucrose preference test,the water consumption proportion at 0-24 h and 0-48 h were(64.7±4.7)% and(73.3±3.0)%,respectively,in CRS group,significantly lower than those[(77.2±2.5)%(t=2.672,P=0.0167)and(83.0±2.8)%(t=2.386,P=0.0297)] in NC group. Although there was no significant difference in the total number of acute seizures[(11.5±1.1)times vs.(13.7±2.1)times;t=0.9767,P=0.3465],mice in CRS group had significantly higher severe seizure score than in control group[(66±10)scores vs.(37±5)scores;t=2.777,P=0.0157]. The seizure onset time was(138±26)s in CRS group,which was significantly shorter than that in NC group[(234±28)s;t=2.485,P=0.0274]. The seizure duration of the CRS group was(61±16)min,which was significantly longer than that of the NC group[(37±5)min;t=3.342,P=0.0053].Conclusion CRS mice are more susceptible to KA-induced acute epileptic seizures.

ESLICARBAZEPINE ACETATE IS ANTIEPILEPTOGENIC IN THE LATRUNCULIN A MOUSE MODEL OF PARTIAL SEIZURES

Although there are many drugs available which have powerful anticonvulsant activity, there is still a high unmet need for antiepileptogenic compounds that prevent the development of chronic epilepsy. Eslicarbazepine acetate (ESL) is a once‐daily (QD) antiepileptic drug (AED) that is converted extensively to eslicarbazepine (a voltage‐gated sodium channel and T‐type calcium channel blocker) after oral administration.1 ESL is a potent anticonvulsant in animal models. Latrunculin A is an actin depolymerization agent that promotes neurotransmitter release in hippocampal synapses and induces multiple action potential firing and increases action potential duration. Latrunculin A hippocampal microperfusion in freely moving mice induces acute epileptic seizures, followed by the occurrence of chronic sporadic spontaneous seizures, in association with changes in extracellular concentrations of excitatory and inhibitory amino acids.2 We have examined ESL for its potential antiepileptogenic activity in preventing the development of chronic partial seizures induced by latrunculin A microperfusion in the mouse hippocampus.Hippocampi of freely‐moving C57BL/6J male mice were continuously perfused with latrunculin A (8 μg/ml, 1 μl/min, 8h/day) for 72 hours. Sham animals received injections of artificial CSF. Forty‐eight‐hours after intrahippocampal latrunculin A infusion, mice were administered either vehicle, 75 mg/kg or 150 mg/kg ESL p.o. once‐daily for three consecutive days. CSF‐infused mice received vehicle. Body temperature and home‐cage locomotor behaviour were assessed four weeks after the end of ESL treatment. Cortical EEG monitoring by telemetry was performed once per week after the end of ESL treatment over a period of six weeks. Data is presented as means ± standard error of the mean (SEM). Data was analyzed using One‐ or Two‐way ANOVA followed by Holm‐Sidak's multiple comparisons test, as appropriate; planned comparison were performed between sham or vehicle (control) and ESL treated groups.Latrunculin A microperfusion in the mouse hippocampus induced electrographic seizures and discharges in the mouse. EEG monitoring showed that transitory ESL treatment within the epileptogenic period caused a sustained significant decrease in the frequency (42 and 74% decrease for 75 and 150 mg/kg ESL versus vehicle at week 4, respectively; 62 and 72% decrease for 75 and 150 mg/kg ESL versus vehicle at week 6, respectively) of epileptiform discharges. There were no significant differences between the two doses of ESL used. Latrunculin A microperfusion and transitory ESL treatment induced no changes in body temperature and locomotor activity, as assessed on week 4 after latrunculin A administration.Transitory oral ESL treatment attenuated sporadic spontaneous electrographic seizures and discharges induced by latrunculin A microperfusion in the mouse hippocampus, supporting a possible anti‐epileptogenic effect of ESL.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy.

Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2) was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ), maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE) depending on the route of KA administration; intracerebral (i.c.) injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p.) injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i) neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH) in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

Association of RASgrf1 methylation with epileptic seizures.

DNA methylation, one of the mechanisms of epigenetic regulation, has been suggested to be related with epilepsy. RASgrf1 is a paternally imprinted gene and has a differentially methylated region (DMR) at the promoter that can silence gene expression. We have previously observed the down-regulation of RASgrf1 in the temporal neocortex of epilepsy patients and in the hippocampus of epileptic animals. Here, we further explored the dynamic change (1-day acute period, 10-day latent period and 45-day chronic phase) of DNA methylation and RASgrf1 expression after acute epileptic seizures in kainic acid (KA)-treated mice, and we observed the impact of N-phthalyl-L-tryptophan (RG108), a DNA methyltransferase (DNMT) inhibitor, on an acute epileptic model by polymerase chain reaction (PCR), western blotting, and bisulfite sequencing PCR (BSP). The results directly showed that the methylation of the RASgrf1 promoter gradually increased and reached a maximal level at the latent period, with subsequent suppression of RASgrf1 mRNA and protein expression levels, which reached a minimum level in the chronic phase. RG108 inhibited the increased methylation of the RASgrf1 gene, with significant inhibition occurring at the latent period, and restored RASgrf1 expression levels in the chronic phase. In addition, we demonstrated that RG108 could suppress acute epileptic seizures in KA-treated mice and epileptic discharges in 4-aminopyridine (4-AP)-treated hippocampal slices. These findings demonstrate that RASgrf1 is closely associated with epilepsy via the aberrant methylation of RASgrf1, and regulating the methylation status of relevant genes might be an intriguing topic in future research on epilepsy.

Dynamic Changes in Spectral and Spatial Signatures of High Frequency Oscillations in Rat Hippocampi during Epileptogenesis in Acute and Chronic Stages.

To analyze spectral and spatial signatures of high frequency oscillations (HFOs), which include ripples and fast ripples (FRs, >200 Hz) by quantitatively assessing average and peak spectral power in a rat model of different stages of epileptogenesis. The lithium-pilocarpine model of temporal lobe epilepsy was used. The acute phase of epilepsy was assessed by recording intracranial electroencephalography (EEG) activity for 1 day after status epilepticus (SE). The chronic phase of epilepsy, including spontaneous recurrent seizures (SRSs), was assessed by recording EEG activity for 28 days after SE. Average and peak spectral power of five frequency bands of EEG signals in CA1, CA3, and DG regions of the hippocampus were analyzed with wavelet and digital filter. FRs occurred in the hippocampus in the animal model. Significant dynamic changes in the spectral power of FRS were identified in CA1 and CA3. The average spectral power of ripples increased at 20 min before SE (p < 0.05), peaked at 10 min before diazepam injection. It decreased at 10 min after diazepam (p < 0.05) and returned to baseline after 1 h. The average spectral power of FRs increased at 30 min before SE (p < 0.05) and peaked at 10 min before diazepam. It decreased at 10 min after diazepam (p < 0.05) and returned to baseline at 2 h after injection. The dynamic changes were similar between average and peak spectral power of FRs. Average and peak spectral power of both ripples and FRs in the chronic phase showed a gradual downward trend compared with normal rats 14 days after SE. The spectral power of HFOs may be utilized to distinguish between normal and pathologic HFOs. Ictal average and peak spectral power of FRs were two parameters for predicting acute epileptic seizures, which could be used as a new quantitative biomarker and early warning marker of seizure. Changes in interictal HFOs power in the hippocampus at the chronic stage may be not related to seizure occurrence.

Targeting brain and peripheral plasticity of the lipidome in acute kainic acid-induced epileptic seizures in mice via quantitative mass spectrometry

Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis have not yet been clarified, and pharmacoresistance exhibited by 30–40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets. For this purpose, we applied a lipidomic strategy to unravel lipid alterations in brain regions, periphery tissues and plasma that are specific for acute epileptic seizures in mice at 1h after seizure induction by systemic kainic acid injection as compared to vehicle controls. Specifically, levels of (i) selected phospholipids and sphingomyelins, (ii) the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), and the endocannabinoid-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), (iii) arachidonic acid (AA), (iv) selected eicosanoids, and (v) fatty acyl content of lipidome were determined in pulverized tissues from six brain regions of kainic acid induced epileptic seizure models and vehicle controls: hypothalamus, hippocampus, thalamus, striatum, cerebellum and cerebral cortex, and from peripheral organs, such as heart and lungs, and in plasma. Alterations in lipid levels after acute epileptic seizures as compared to non-seizure controls were found to be brain region- and periphery tissue-specific, including specific plasma lipid correlates, highlighting their value as marker candidates in translational research studies, and/or drug discovery and response monitoring.

Medical management of epileptic seizures: challenges and solutions.

Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs), with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical–psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and “pseudoseizure” patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who deals with the acute management of seizures may encounter. The document also highlights the numerous avenues for new research that would help practitioners optimize epilepsy management.

Symptoms and characteristics of individuals with profound hyponatremia: a prospective multicenter observational study.

To assess symptoms and characteristics of hyponatremia, the most common electrolyte disturbance in hospitalized individuals and a condition that is associated with substantial morbidity and mortality. Prospective observational multicenter study. Two Swiss academic centers. Individuals with profound hypoosmolar hyponatremia (sodium<125 mmol/L) (N=298). All symptoms and complete medical history including current medications, therapy management, and in-hospital outcomes were recorded. The median age of all participants was 71 (interquartile range (IQR) 60-80), 195 (65%) were female, and mean serum sodium value on admission was 120 mmol/L (IQR 116-123 mmol/L). Frequent clinical symptoms were nausea (n=130, 44%), acute vomiting (n=91, 30%), generalized weakness (n=205, 69%), fatigue (n=175, 59%), gait disturbance (n=92, 31%), recurrent falls (n=47, 16%), and acute falls (n=60, 20%). Fractures were reported in 11 participants (4%). More-severe symptoms such as acute epileptic seizures and focal neurological deficits were identified in 16 (5%) and 17 (5%) participants, respectively. The most common comorbidities were hypertension (n=199, 67%), congestive heart failure (n=44, 15%), chronic renal failure (n=64, 21%), pulmonary disease (82, 28%), and central nervous system disease (n=114, 38%). During hospitalization, 12 (4%) participants died, and 103 (35%) needed treatment in the intensive care unit. A wide spectrum of symptoms accompanies profound hyponatremia. Most participants had moderate symptoms mirroring chronic hyponatremia with brain cell adaptation. Participants with profound hyponatremia had several comorbidities.

Effects of eslicarbazepine acetate on acute and chronic latrunculin A-induced seizures and extracellular amino acid levels in the mouse hippocampus.

BackgroundLatrunculin A microperfusion of the hippocampus induces acute epileptic seizures and long-term biochemical changes leading to spontaneous seizures. This study tested the effect of eslicarbazepine acetate (ESL), a novel antiepileptic drug, on latrunculin A-induced acute and chronic seizures, and changes in brain amino acid extracellular levels. Hippocampi of Swiss mice were continuously perfused with a latrunculin A solution (4 μM, 1 μl/min, 7 h/day) with continuous EEG and videotape recording for 3 consecutive days. Microdialysate samples were analyzed by HPLC and fluorescence detection of taurine, glycine, aspartate, glutamate and GABA. Thereafter, mice were continuously video monitored for two months to identify chronic spontaneous seizures or behavioral changes. Control EEG recordings (8 h) were performed in all animals at least once a week for a minimum of one month.ResultsOral administration of ESL (100 mg/kg), previous to latrunculin A microperfusion, completely prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity. Hippocampal extracellular levels of taurine, glycine and aspartate were significantly increased during latrunculin A microperfusion, while GABA and glutamate levels remained unchanged. ESL reversed the increases in extracellular taurine, glycine and aspartate concentrations to basal levels and significantly reduced glutamate levels. Plasma and brain bioanalysis showed that ESL was completely metabolized within 1 h after administration to mainly eslicarbazepine, its major active metabolite.ConclusionESL treatment prevented acute latrunculin A-induced seizures as well as chronic seizures and all EEG chronic signs of paroxysmal activity, supporting a possible anti-epileptogenic effect of ESL in mice.

Effect of lacosamide on structural damage and functional recovery after traumatic brain injury in rats

In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post-TBI structural or functional impairment. Composite neuroscore in the TBI-LCM group lagged behind that in the TBI-Veh group at 15 d post-injury, but no compromise was found in other indices of post-TBI recovery in the LCM treated animals.

P75 – 1611 Midazolam oromucosal solution versus rectal diazepam for prolonged acute convulsive epileptic seizures: Italian cost-effectiveness analysis

P75 – 1611 Midazolam oromucosal solution versus rectal diazepam for prolonged acute convulsive epileptic seizures: Italian cost-effectiveness analysis

P78 – 1596 The cost effectiveness of midazolam oromucosal solution for the treatment of prolonged acute convulsive epileptic seizures in France

P78 – 1596 The cost effectiveness of midazolam oromucosal solution for the treatment of prolonged acute convulsive epileptic seizures in France

Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy

Scorpion venom is a traditional antiepileptic medicine in Asia. We examined the effects of scorpion venom heat-resistant protein (SVHRP) on seizure behavior of rats with kainate-induced epilepsy and expression of proenkephalin (pENK) in their hippocampus. Subcutaneous injections of convulsive doses of kainic acid (KA, 10 mg/kg) evoked acute epileptic seizures; the intensity of such seizures was measured after subsequent injections of lower (subthreshold in the norm) doses of KA (5 mg/kg). Scorpion venom heat-resistant protein in a dose of 125 μg/kg was given in a part of the animals through i.p. injections daily during 10 days; rats of the control groups were injected with normal saline. Behavioral indices were measured, and the hippocampus was taken for pENK mRNA estimation by RT-PCR analysis. The mean behavioral score of seizure sensitivity in the SVHRP-treated group was smaller significantly (P < 0.05) compared to that in the control group (1.19 vs 2.93). The pENK mRNA level was dramatically greater in hippocampal neurons of KA-treated rats with a high seizure sensitivity, while in the SVHRP-treated group the respective index was significantly lower. Thus, SVHRP inhibits behavioral seizures in epilepsy and reverses the abnormally increased pENK mRNA in hippocampal neurons of such animals.