Seizure Severity In Rats Research Articles

The Effects of Prenatal Norharman Exposure on Seizure Severity in Rats

Background: Norhraman is an alkaloid that can damage the nervous system. Objective: This experimental study aimed to investigate the effects of prenatal norharman exposure on seizure severity in adult rats. Methods: A total of 36 Wistar rats were randomly divided into 3 groups as follows: Control, sham (solvent), and norharman (1000 ug/kg). The sham and norharman groups were treated once daily for 8-18 of the fetal period. 2 months after birth, kindling was performed by the daily injection of Pentylenetetrazol (PTZ) (30 mg/kg); then, the seizure behavior was recorded for approximately 30 minutes. The obtained data were analyzed using Analysis of Variance (ANOVA) and Tukey’s posthoc test. Results: The present study data indicated that administrating norharman in the fetal period increased seizure responses to PTZ, i.e., significant in the examined female rats (P<0.05). Conclusion: According to the current research findings, the severity of seizures increases in subjects who have been exposed to norharman during the prenatal period.

Neuromodulation treatments for ADHD: The ABCs of eTNS

Free AccessNeuromodulation treatments for ADHD: The ABCs of eTNSSandra Loo and James McGoughSandra LooSearch for more papers by this author and James McGough1 Professor in Residence in the Division of Child and Adolescent Psychiatry and the Center for Neurobehavioral Genetics at the Semel Institute for Neuroscience and Human Behavior in Los Angeles, CA. She also serves on the Advisory Board of the ADHD Report. She can be reached at: [email protected].2 Professor of Clinical Psychiatry at the Semel Institute for Neuroscience and Human Behavior and David Geffen School of Medicine at UCLA in Los Angeles, CA. Neither of the principal investigators (James McGough, M.D. or Sandra Loo, Ph.D.) have any financial stake or financial relationship in the product or company.Search for more papers by this authorPublished Online:February 2020https://doi.org/10.1521/adhd.2020.28.1.8PDFPDF PLUS ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations AboutREFERENCESCook I. A., , Espinoza R., , Leuchter A. F. (2014). Neuromodulation for depression: Invasive andnoninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nervestimulation). Neurosurgery Clinics of North America; 25, 103–116. Crossref, Google ScholarFaraone S. V. (2009). Using meta-analysis to compare the efficacy of medications for Attention-Deficit/Hyperactivity Disorder in youths. Pharmacy and Therapeutics, 34(12), 678–683, 694. Google ScholarFood and Drug Administration. (2019, April 19). FDA permits marketing of first medical device for treatment of ADHD [Press release]. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-medical-device-treatment-adhd Google ScholarGoode A. P., , Coeytaux R., , Maslow G., , Davis N., , Hill S., , Namdari B., , & Kemper A. (2018). Nonpharmacologic treatments for Attention-Deficit/Hyperactivity Disorder: A systematic review. Pediatrics, 141(6), e20180094. Crossref, Google ScholarHuster R. J., , Enriquez-Geppert S., , Lavalle C. F., , Falkenstein M., , & Herrmann C. S. (2013). Electroencephalography of response inhibition tasks: functional networks and cognitive contributions. International Journal of Psychophysiology, 87, 217–233. Crossref, Google ScholarLoo S. K., , & McGough J. J. (October, 2019). Trigeminal nerve stimulation for ADHD: Correlates and predictors of treatment response. Paper presented at the American Academy of Child and Adolescent Psychiatry meeting, Chicago, IL. Google ScholarMercante B., , Enrico P., , Floris G., , Quartu M., , Boi M., , Pina Serra M., … & Deriu F. (2017). Trigeminal nerve stimulation induces FOS immunoreactivity in selected brain regions, increased hippocampal cell proliferation and reduces seizure severity in rats. Neuroscience, 361, 69–80. Crossref, Google ScholarMcGough J. J., , Loo S. K., , Sturm A., , Cowen J., , Leuchter A. F., , & Cook I. A. (2015), An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulant in youth with Attention-Deficit/Hyperactivity Disorder. Brain Stimulation; 8, 299–304. Crossref, Google ScholarMcGough J. J., , Sugar C., , Sturm A., , Salgari G., , Cowen J., , Leuchter A. F., , Cook I. A., , & Loo S. K., (2019). Double-blind, sham-controlled, pilot study of trigeminal nerve stimulation (TNS) for Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 58(4), 403–411 Crossref, Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 28Issue 1Feb 2020 Information© 2020 The Guilford PressPDF download

The role of the GLP-1/GLP-1R signaling pathway in regulating seizure susceptibility in rats

ObjectiveThis study aimed to investigate the role of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor(R) signaling in the regulation of seizure susceptibility and to explore the potential mechanism in rats. MethodsHyperthermia-induced seizures in SD rats were generated using hot bath methods, and seizure severity was measured according to Racine scores and electroencephalogram (EEG). Protein levels of GLP-1 and GLP-1R in the brain tissues of rats were evaluated through ELISA, western blot analysis, and immunohistochemistry to explore the possible roles of each in FS. Neuronal excitability, spontaneous inhibitory postsynaptic currents (sIPSCs) and transient receptor potential cation channel subfamily V member 1(TRPV1) currents were tested using the patch-clamp method in cultured hippocampal neurons. ResultSignificant decreases in the levels of GLP-1 and GLP-1R were observed in the hippocampi of rats compared to those in the control group. Furthermore, treatment with the GLP-1R pharmacological inhibitor exendin9-39 increased hyperthermia- induced seizure severity in rats and promoted neuronal firing activity in cultured neurons. Importantly, exendin9-39 and GLP-1R knockdown decreased the amplitude and frequency of sIPSCs in cultured neurons. In addition, GLP-1R knockdown elevated downstream TRPV1 expression and promoted capsaicin-induced TRPV1 function, which may regulate inhibitory neurotransmission to affect seizure susceptibility. ConclusionThe present study suggests that inhibition of GLP-1R signaling promotes seizure activity, which plays a key role in the pathogenesis of FS.

Indispensable Amino Acid–Deficient Diets Induce Seizures in Ketogenic Diet–Fed Rodents, Demonstrating a Role for Amino Acid Balance in Dietary Treatments for Epilepsy

Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for≥7 d, and tested for seizures using various stimuli. Microchip analysis of rat APCs was also used to determine if changes in transcripts for structures relevant to seizurogenesis are affected by a ThrDev diet. Glutamate release was measured in microdialysis samples from APCs during the first meal after 7 d on a CD or a ThrDev diet. Adult rats showed increased susceptibility to seizures in both chemical (58%) and electroshock (doubled) testing after 7 d on a ThrDev diet compared with CD (each trial, P≤ 0.05). Seizure-prone Mongolian gerbils had fewer seizures after receiving a KD, but exacerbated seizures (68%) after 1 meal of KD minus Thr (KD-T compared with CD, P<0.05). In kindled rats fed KD-T, both counts (19%) and severities (77%) of seizures were significantly elevated (KD-T compared with CD, P<0.05). Gene transcript changes were consistent with enhanced seizure susceptibility (7-21 net-fold increases, P=0.045-0.001) and glutamate release into the APC was increased acutely (4-fold at 20 min, 2.6-fold at 60 min, P<0.05) after 7 d on a ThrDev diet. Seizure severity in rats and gerbils was reduced after KDs and exacerbated by ThrDev, both in KD- and CD-fed animals, consistent with the mechanistic studies. We suggest that a complete protein profile in KDs may improve IAA balance in the APC, thereby lowering the risk of seizures.

Trigeminal nerve stimulation induces Fos immunoreactivity in selected brain regions, increases hippocampal cell proliferation and reduces seizure severity in rats

Sites and mechanisms by which trigeminal nerve stimulation (TNS) exerts beneficial effects on symptoms of drug-resistant epilepsy and depression are still unknown. Effects of short-term TNS on brain regions involved in the physiopathology of these disorders were investigated in this study.Forty male rats were assigned to three groups: TNS (undergoing electrical stimulation of the left infraorbitary nerve via surgically implanted cuff electrodes); Sham (undergoing surgical procedure but without a stimulation); Naïve rats. The effects of TNS (3-hour session; 30-s ON, 5-min OFF; 30Hz; 500μs; 2mA) were evaluated on: (i) behavioral pattern of pentylenetetrazole (PTZ)-induced seizures as measured by the Racine scale; (ii) c-Fos-like immunoreactivity in discrete brain areas; (iii) hippocampal cell proliferation by bromodeoxyuridine (BrdU)-like immunoreactivity.In comparison with Sham groups, TNS significantly decreased the duration of PTZ-induced seizures (p<0.05) and promoted a faster recovery (p<0.001) by reducing the most severe seizure types. In the TNS group the number of c-Fos-labeled cells was significantly increased (p<0.001) in the trigeminal nuclear complex, nucleus of the solitary tract, locus coeruleus, dorsal raphe nucleus, hippocampus, amygdala, endopiriform nucleus, entorhinal cortex and sensorimotor cortex. In the TNS group the number of BrdU-positive cells in the dentate gyrus was significantly greater with respect to both Naïve and Sham groups.Data show that acute TNS effectively counteracted PTZ-induced seizures and boosted hippocampal cell proliferation in rats. TNS increased c-Fos-like immunoreactivity in brainstem and forebrain structures which play a pivotal role in the physiopathology of epilepsy and depression.

Correlation between peripheral blood inflammatory cytokines and kainic acid-induced seizure severity in rats

Objectives To investigate the correlation between the level of peripheral blood inflammatory cytokines and kainic acid-induced seizure severity in rats. Methods 140 rats were divided into control and model group randomly, 70 rats in each group. Model group rats were injected with kainic acid (10 mg/kg) by intraperitoneal, and the control rats were injected with sodium chloride.The change of their behaviors was observed and the concentrations of TNF-α, IL-1β, IL-4 and IL-10 were determined by ELISA in each group at different times. Results The rats showed epilepsy grand mal in 3 h-9 h after KA injection . The concentrations of TNF-α and IL-1β in model groups were significantly higher than those in control group in 6 h-12 h(6 h: (21.5±3.2)pg/ml vs (12.3±3.1)pg/ml; 12 h: (20.6±4.2)pg/ml vs (11.5±3.8)pg/ml)(P 0.05). Conclusion The proinflammatory cytokines (TNF-α and IL-1β) participate in the seizure procedure, meanwhile their levels and seizure severity have eminent correlations, but antiinflammatory cytokines (IL-4 and IL-10) had not. Key words: Kainic acid; Epilepsy; Seizure severity; Inflammatory cytokines

Anticonvulsant effect of fisetin by modulation of endogenous biomarkers

Epilepsy is a group of disorders of the central nervous system (CNS) bearing its pathological origin in paroxysysmal cerebral dysrhythmia, clinically consisting episodes (seizure) of loss of consciousness. Fisetin is a tetrahydroxy flavone that possesses antiyperlipidemic, antioxidant, anti-inflammatory and antidiabetic potential. The aim of present investigation was to investigate the anticonvulsant activity of fisetin (5, 10 and 25mg/kg) against pentylenetetrazole (PTZ), strychnine (STR), isoniazid (INH) and maximal electroshock (MES) induced convulsions in mice as well as electrical kindling seizures in rats. Diazepam and phenytoin were used as reference anticonvulsant drugs for comparison. Intraperitoneal administration of PTZ (90mg/kg), strychnine (5mg/kg) and isoniazid (300mg/kg) resulted in hind limb, tonic-clonic convulsion along with lethality in mice, whereas twice daily auricular stimulation resulted progressive severity of seizures in rats. It also significantly altered levels of brain gamma amino butyric acid (GABA) along with nitric oxide (NO) and xanthine oxidase (XO) in mice. Treatment with fisetin (10 and 25mg/kg) delayed onset of convulsion along with duration of tonic-clonic convulsions as well as it significantly reduced PTZ and STR-induced mortality in mice (P<0.05 – P<0.001). It also significantly (P<0.001) reduced severity of electrically kindled seizures in rats and total number of rats seizure per group. Mice treated with fisetin (10 and 25mg/kg) significantly increased level of brain GABA whereas it significantly decreased elevated level of brain NO and XO. In conclusion, the findings of present study provide pharmacological credence to anticonvulsant profile of fisetin. The protection against the convulsions and restoration of endogenous enzyme level give an innuendo to its probable mechanism of action which may be mediated through the GABAergic pathway and inhibition of oxidative injury.

Delta sleep-inducing peptide attenuates severity of lindane-induced seizures in rats

Delta sleep-inducing peptide attenuates severity of lindane-induced seizures in rats

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30 s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.

α-Noradrenaline modulation of D,L-allylglycine seizures

The preferential α 2-noradrenergic agonist clonidine dose-relatedly increased the onset of seizures and mortality times, and decreased seizure severity in rats treated with D,L-allylglycine. These effects were reduced by a dose (2.5 mg/kg) of the preferential α 2-antagonist yohimbine, which was itself inactive on the allylglycine seizures. Yohimbine 10 mg/kg alone decreased onset and mortality times. The preferential α 1-antagonist prazosin had a slight anticonvulsant effect. These results suggest that the reduction of NA release at α 2-noradrenergic receptors or antagonism of noradrenaline effects at α 1-receptors exerts seizure suppressant effects.

Reduction of duration and severity of megimide seizures in rats on a folic acid deficient diet.

Folic acid deficient diet reduces the duration and severity of intravenous megimide seizures in the rat after 6 months of diet. Plasma and serum folate levels are strongly reduced after that period. The difference between Lactobacillus casei and Streptococcus faecalis activity in brain show a slight, but not significant, decrease after 12 months of diet.