The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification differentiation novel ASDs mice, corresponding assay rats has not been developed. We established method seizure induction rats, with behaviors similar to those observed mice including head nod, jaw clonus, forelimb clonus.A convulsive current that elicits these 97% (CC97 ) was determined using Probit...

Abstract Objective Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In clinic, individuals DS often present first febrile seizure and, subsequently, generalized tonic‐clonic seizures can continue throughout life. To facilitate development ASDs for DS, contract site National Institute Neurological Disorders and Stroke (NINDS) Epilepsy...

The formation of 24S-hydroxycholesterol is a brain-specific mechanism cholesterol catabolism catalyzed by 24-hydroxylase (CYP46A1, also known as CH24H). CH24H has been implicated in various biological mechanisms, whereas pharmacological lowering not fully studied. Soticlestat novel small-molecule inhibitor CH24H. Its therapeutic potential was previously identified mouse model with an epileptic phenotype. In the present study, anticonvulsive property soticlestat characterized rodent models...

Edema is an important target for clinical intervention after traumatic brain injury (TBI). We used in vivo cellular resolution imaging and electrophysiological recording to examine the ionic mechanisms underlying neuronal edema their effects on network excitability controlled cortical impact (CCI) mice. Unexpectedly, we found that 48 hours CCI was associated with reduced excitability, concurrent increase expression ratio of cation-chloride cotransporters (CCCs) NKCC1 KCC2. Treatment CCC...

Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this developing animals. We focused on seven age groups both male and female rats. Biphasic pulses with 0.3 ms duration current intensities from 20 to 80 mA were applied transcorneally for 3 s calculate threshold individual groups. Threshold intensity necessary elicitation clonic seizures was highly age- sex-dependent. The...

Status epilepticus (SE) is a seizure or series of seizures that persist for >30 min and often results in mortality. Death rarely occurs during immediately following activity, but usually within 30 days. Although ventricular arrhythmias have been implicated SE-related mortality, the effects this prolonged activity on cardiac function susceptibility to not directly investigated. We evaluated myocardial damage, alterations electrical experimentally induced produced by SE rats. resulted...

The lamotrigine-resistant amygdala kindling model uses repeated administration of a low dose lamotrigine during the process to produce resistance lamotrigine, which also extends some other antiseizure drugs (ASDs). This pharmacoresistant epilepsy has been incorporated into testing scheme utilized by Epilepsy Therapy Screening Program (ETSP). Although ASDs have evaluated in this model, comprehensive evaluation ASD prototypes not reported.Following depth electrode implantation and recovery,...

Abstract Objective Approximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied evaluating efficacy following a single administration test compound in either acute electrical or chemical induction. However, the use animal models spontaneous seizures and repeated compounds may better differentiate compounds. Therefore, this approach been instituted as part National Institute...

Cannabidiolic acid (CBDa) is pharmacologically unique from cannabidiol (CBD), but its chemical instability poses challenges for potential clinical utility. Here, we used magnesium ions to stabilize two cannabidiolic acid-enriched hemp extracts (Mg-CBDa and Chylobinoid, the latter of which also contains minor cannabinoid constituents) compared their anticonvulsant activities with CBD in maximal electroshock seizure test (MES) rats.Sprague-Dawley rats received intraperitoneal (i.p.) injections...

Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice results handling-induced seizures and is useful for evaluating compounds effective against infection-induced seizures. However, to date only a few have been evaluated this model, comprehensive study of antiseizure medications (ASMs) has not yet performed. Furthermore, as the TMEV infection produces marked neuroinflammation, an evaluation prototype anti-inflammatory needed well.Male were inoculated (day 0)...

Original Article Abstract: Citation: Feng H, Clatot J, Kaneko K, Flores-Mendez M, Wengert ER, Koutcher C, Hoddeson E, Lopez Lee D, Arias L, Liang Q, Zhang X, Somarowthu A, Covarrubias Gunthorpe MJ, Large CH, Akizu N, Goldberg EM. Targeted therapy improves cellular dysfunction, ataxia, and seizure susceptibility in a model of progressive myoclonus epilepsy. Cell Reports Medicine , Volume 5, Issue 2, 2024, 101389. The recurrent variant KCNC1 -p.Arg320His causes epilepsy type 7 (EPM7), defined...

Summary Objective Approximately 30% of patients with epilepsy are refractory to existing antiseizure drugs ( ASD s). Given that the properties central nervous systems these likely be altered due their epilepsy, tissues from rodents have undergone epileptogenesis might provide a therapeutically relevant disease substrate for identifying compounds capable attenuating pharmacoresistant seizures. To facilitate development such model, this study describes effects classical glutamate receptor...

The discovery and development of novel antiseizure drugs (ASDs) that are effective in controlling pharmacoresistant spontaneous recurrent seizures (SRSs) continues to represent a significant unmet clinical need. Epilepsy Therapy Screening Program (ETSP) has undertaken efforts address this need by adopting animal models the salient features human epilepsy employing these for preclinical testing investigational ASDs. One such model garnered increased interest recent years is mouse variant...

Objective Sudden Unexpected Death in Epilepsy (SUDEP) accounts for 20% of mortality those with recurrent seizures. While risk factors, monitoring systems, and standard practices are place, the pathophysiology SUDEP is still not well understood. Better knowledge its potential mechanisms action crucial to reducing this patient population developing treatment options. Clinical studies animal models suggest that diminished post-ictal respiratory control may be dominant mechanism contributing...

The metabotropic glutamate receptor subtype 2 (mGlu2 ) possesses both orthosteric and allosteric modulatory sites, are expressed in the frontal cortex limbic structures, can affect excitatory synaptic transmission. Therefore, mGlu2 is a potential therapeutic target treatment of epilepsy. present study seeks to evaluate anticonvulsant -acting compounds.The efficacy two selective -positive modulators (PAMs) (JNJ-42153605 JNJ-40411813/ADX71149) one mGlu2/3 agonist (LY404039) were evaluated...

Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer means to deliver behavioral, psychosocial, disease self-management music-based interventions improve therapy outcomes for chronic diseases, including pain epilepsy. To explore new translational opportunities in developing digital neurological disorders, their integration with pharmacotherapies, we examined analgesic antiseizure effects of specific musical compositions mouse models The music...

Despite the availability of more than 25 antiseizure drugs on market, approximately 30% patients with epilepsy still suffer from seizures. Thus, therapy market has a great need for breakthrough drug that will aid pharmacoresistant patients. In our previous study, we discovered vitamin K analogue, 2h, which displayed modest activity in zebrafish and mouse seizure models. However, there are limitations to this compound due its pharmacokinetic profile. develop new series analogues by modifying...

Status epilepticus (SE) activates the autonomic nervous system, increasing sympathetic system control of cardiac function during seizure activity. However, lasting effects SE on regulation heart, which may contribute to mortality following activity, are unknown. Therefore, was assessed SE.Using Sprague-Dawley rats after 1-2 weeks recovery from lithium-pilocarpine-induced or procedures, we tested overall sympathovagal individual contributions and parasympathetic components baroreflex...

We previously demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate subtype 2 (mGlu2 ) receptors have potential synergistic interactions with the antiseizure drug levetiracetam (LEV). The present study utilizes isobolographic analysis to evaluate combined administration JNJ-46356479, a selective and potent mGlu2 PAM, LEV as well sodium valproate (VPA) lamotrigine (LTG).The anticonvulsant efficacy JNJ-46356479 was evaluated in 6-Hz model psychomotor seizures mice....