Tags

Type your tag names separated by a space and hit enter

Loss of Protection by Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus is Mediated via Inflammatory Signalling.
Neuroscience. 2020 Jun 24; 442:1-16.N

Abstract

The evidences from various studies show the association of peripheral and neuronal inflammation with complex pathophysiology of status epilepticus (SE). In this view, the present work attempted to develop a model of neuronal inflammation mediated SE by combining both epileptic and inflammatory components of the disease and also to mimic SE co-morbid with systemic inflammation by peripheral administration of the lipopolysaccharide (LPS) 2 h prior to the pilocarpine (PILO) induction in C57BL/6 mice. We evaluated the anti-convulsant and neuroprotective effects of 7-day prophylactic treatment with three conventional anti-epileptic drugs (Sodium valproate, SVP 300 mg/kg p.o.; Carbamazepine CBZ 100 mg/kg p.o.; Levetiracetam; LEV 200 mg/kg p.o.) of widespread clinical use. Morris water maze and Rota rod tests were carried out 24-h post-exposure to evaluate the neurobehavioral co-morbidities associated with neuroinflammation-mediated status epilepticus. Upon priming with LPS, the loss of protection against PILO-induced seizures was observed by SVP and CBZ, however, LEV showed protection by delaying the seizures. Dramatic elevation in the seizure severity and neuronal loss demonstrated the possible pro-convulsant effect of LPS in the PILO model. Also, the decreased cytokine levels by the AEDs showed their association with NF-κB, IL-1β, IL-6, TNF-α and TGF-β pathways in PILO model. The loss of protective activities of SVP and CBZ in LPS+PILO model was due to increased cytokine levels associated with over-activation of neuroinflammatory pathways, however, partial efficacy of LEV is possibly due to association of other neuroinflammatory mechanisms. The current work provides direct evidence of the contribution of increased peripheral and neuronal inflammation in seizures via regulation of inflammatory pathways in the brain.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.Defense Institute of Physiology & Allied Science, Defense Research and Development Organization, New Delhi, India.Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. Electronic address: dvohra@jamiahamdard.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32592825

Citation

Vyas, Preeti, et al. "Loss of Protection By Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus Is Mediated Via Inflammatory Signalling." Neuroscience, vol. 442, 2020, pp. 1-16.
Vyas P, Tulsawani RK, Vohora D. Loss of Protection by Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus is Mediated via Inflammatory Signalling. Neuroscience. 2020;442:1-16.
Vyas, P., Tulsawani, R. K., & Vohora, D. (2020). Loss of Protection by Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus is Mediated via Inflammatory Signalling. Neuroscience, 442, 1-16. https://doi.org/10.1016/j.neuroscience.2020.06.024
Vyas P, Tulsawani RK, Vohora D. Loss of Protection By Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus Is Mediated Via Inflammatory Signalling. Neuroscience. 2020 Jun 24;442:1-16. PubMed PMID: 32592825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of Protection by Antiepileptic Drugs in Lipopolysaccharide-primed Pilocarpine-induced Status Epilepticus is Mediated via Inflammatory Signalling. AU - Vyas,Preeti, AU - Tulsawani,Raj Kumar, AU - Vohora,Divya, Y1 - 2020/06/24/ PY - 2019/12/05/received PY - 2020/06/16/revised PY - 2020/06/17/accepted PY - 2020/6/28/pubmed PY - 2020/6/28/medline PY - 2020/6/28/entrez KW - antiepileptic drugs KW - cognition KW - cytokine release KW - inflammation KW - lipopolysaccharide KW - pilocarpine-induced status epilepticus SP - 1 EP - 16 JF - Neuroscience JO - Neuroscience VL - 442 N2 - The evidences from various studies show the association of peripheral and neuronal inflammation with complex pathophysiology of status epilepticus (SE). In this view, the present work attempted to develop a model of neuronal inflammation mediated SE by combining both epileptic and inflammatory components of the disease and also to mimic SE co-morbid with systemic inflammation by peripheral administration of the lipopolysaccharide (LPS) 2 h prior to the pilocarpine (PILO) induction in C57BL/6 mice. We evaluated the anti-convulsant and neuroprotective effects of 7-day prophylactic treatment with three conventional anti-epileptic drugs (Sodium valproate, SVP 300 mg/kg p.o.; Carbamazepine CBZ 100 mg/kg p.o.; Levetiracetam; LEV 200 mg/kg p.o.) of widespread clinical use. Morris water maze and Rota rod tests were carried out 24-h post-exposure to evaluate the neurobehavioral co-morbidities associated with neuroinflammation-mediated status epilepticus. Upon priming with LPS, the loss of protection against PILO-induced seizures was observed by SVP and CBZ, however, LEV showed protection by delaying the seizures. Dramatic elevation in the seizure severity and neuronal loss demonstrated the possible pro-convulsant effect of LPS in the PILO model. Also, the decreased cytokine levels by the AEDs showed their association with NF-κB, IL-1β, IL-6, TNF-α and TGF-β pathways in PILO model. The loss of protective activities of SVP and CBZ in LPS+PILO model was due to increased cytokine levels associated with over-activation of neuroinflammatory pathways, however, partial efficacy of LEV is possibly due to association of other neuroinflammatory mechanisms. The current work provides direct evidence of the contribution of increased peripheral and neuronal inflammation in seizures via regulation of inflammatory pathways in the brain. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/32592825/Loss_of_protection_by_antiepileptic_drugs_in_lipopolysaccharide-primed_pilocarpine-induced_status_epilepticus_is_mediated_via_inflammatory_signalling L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(20)30400-0 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.