Neurochem Res. Jul;42(7) doi: /sz. Epub Mar Animal Models of Seizures and Epilepsy: Past, Present, and. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will. This chapter considers ethical issues of major importance in the use of animal models in seizure and epilepsy research. The chapter discusses the nature.
Epilepsy and Models Animal Seizures of
The efficacy of the Vitamin D3 treatment in reducing seizures was determined by comparing the number of seizures experienced during the 90 days prior to treatment onset to the number of seizures experienced in the 90 days after treatment onset. The existing clinical evidence suggests a therapeutic effect of Vitamin D3 in human epilepsy, but there is a need for larger Phase I trials and Phase II randomized, placebo-controlled trials to investigate optimal dosing and short-term and long-term efficacy.
Vitamin D3 status is strongly associated with risk of sudden cardiac death in heart disease and patients with severe kidney disease on hemodialysis. Common to severe heart and kidney disease is impaired heart rate variability HRV , particularly vagus-mediated high-frequency HRV 69 — The weight of evidence from basic research and animal models over the past several decades supports an anticonvulsant effect of Vitamin D3.
Epidemiological data as well as a variety of case studies also point to a connection between Vitamin D3 and epilepsy and support the use of Vitamin D3 as a potential therapy for human epilepsy, both in its own right and in conjunction with existing AEDs.
Despite these limitations, existing clinical data have, in the opinion of this review, been positive enough to warrant larger Phase I and Phase II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D3 as a treatment for human epilepsy.
The authors have contributed to the preparation, research, and writing of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study was supported by a generous grant from Beverly and James Peters and family, as well as from Linda and Robert Brill and family. Kwan P, Brodie MJ. Early identification of refractory epilepsy.
N Engl J Med Excess mortality and hospitalized morbidity in newly treated epilepsy patients. Meier C, Kraenzlin ME. Antiepileptics and bone health. Ther Adv Musculoskelet Dis 3: A controlled pilot study. Br Med J 2: Administration of 1, dihydroxyvitamin D 3 results in the elevation of hippocampal seizure threshold levels in rats.
Brain Res Anticonvulsant effects of 1, dihydroxyvitamin D in chemically induced seizures in mice. Brain Res Bull Increased severity of chemically induced seizures in mice with partially deleted vitamin D receptor gene.
Neurosci Lett Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock. Eur J Pharmacol Effect of cholecalciferol on the anticonvulsant action of some second generation antiepileptic drugs in the mouse model of maximal electroshock.
Pharmacol Rep Correction of vitamin D deficiency improves seizure control in epilepsy: Epilepsy Behav Neurosteroid vitamin D system as a nontraditional drug target in neuropsychopharmacology. Behav Pharmacol NIH office of Dietary Supplements. Fact Sheet for Professionals. New clues about vitamin D functions in the nervous system.
Trends Endocrinol Metab Optimal vitamin D supplemental levels for cardiovascular disease protection. Dis Markers 8: Kalueff AV, Tuohimaa P. Neurosteroid hormone vitamin D and its utility in clinical nutrition. The prevalence of hypovitaminosis D among US adults: Ethn Dis PubMed Abstract Google Scholar.
Arch Neurol Serum vitamin D and the risk of Parkinson disease. J Neurol Sci Vitamin D intake and incidence of multiple sclerosis. Schizophrenia, vitamin D, and brain development. Int Rev Neurobiol Increased anxiety in mice lacking Vitamin D receptor gene. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol Vitamin D hormone confers neuroprotection in parallel with down regulation of L-type calcium channel expression in hippocampal neurons.
J Neurosci Mechanisms of neuroprotective action of vitamin D3. Vitamin D3 and brain development. Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development. Brain Res Dev Brain Res Banerjee P, Chaterjee M. Anti-proliferative role of vitamin D and its analogs — a brief overview. Mol Cell Biochem Developmental vitamin D3 deficiency alters the adult rat brain.
Evidence of functional vitamin D receptors in rat hippocampus. Rat oligodendrocytes express the vitamin D 3 receptor and respond to 1,dihydroxyvitamin D 3. Distribution of 1,dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord.
J Chem Neuroanat Distribution of 1,dihydroxyvitamin D3 receptor immunoreactivity in the limbic system of the rat. Horm Metab Res A ChIP-seq defined genome-wide map of vitamin D receptor binding: Genome Res The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. Cytokines and neuronal ion channels in health and disease. Vezzani A, Baram TZ.
New roles of interleukin-1 beta in the mechanisms of epilepsy. Epilepsy Curr 7: Nat Neurosci 4: Cytokine effects on glutamate uptake by human astrocytes. J Pharmacol Exp Ther Control of synaptic strength by glial TNFalpha. Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats.
Potent inhibitory effects of glial-derived neurotrophic factor against kainic acid mediated seizures in the rat. Continuous induction of neurotrophin-3 triggers sprouting, decreases the levels of TrkA and TrkC, and inhibits epileptogenesis and activity-dependent axonal growth in adult rats. Seizure suppression by GDNF gene therapy in animal models of epilepsy. Mol Ther Leranth C, Ribak CE. Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: Exp Brain Res Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity.
The rapid effects of 1,dihydroxyvitamin D3 require the vitamin D receptor and influence hydroxylase activity: J Biol Chem Mol Cell Endocrinol Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. Rapid modulation of osteoblast ion channel response by 1alpha,25 OH 2-vitamin D3 requires the presence of a functional vitamin D nuclear receptor. Jia Z, Nemere I. Immunochemical studies on the putative plasmalemmal receptor for 1, dihydroxyvitamin D3 II.
Epilepsy Curr ;9 3: Modeling new therapies for infantile spasms. Baram TZ, Schultz L. Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat. Brain Res Dev Brain Res ;61 1: Blockade of neuronal activity during hippocampal development produces a chronic focal epilepsy in the rat. J Neurosci ;20 8: Amiloride but not memantine reduces neurodegeneration, seizures and myoclonic jerks in rats with cardiac arrest-induced global cerebral hypoxia and reperfusion.
PLoS One ;8 4: Alkdogan I, Yonguc NG. Experimental epilepsy models and morphologic alterations of experimental epilepsy models in brain and hippocampus. Underlying Mechanisms of Epilepsy. In Tech publishers; Pentylenetetrazol-induced kindling in rats: Pharmacol Biochem Behav ;40 2: The kainic acid model of temporal lobe epilepsy.
Neurosci Biobehav Rev ;37 10 Pt 2: Epilepsia ;54 Suppl 2: Effect of the selective N-methyl-D-aspartate receptor agonist 3- 2-carboxypiperazinyl propylphosphonic acid on [3H]flunitrazepam binding. Eur J Pharmacol ; 1: Interictal spikes precede ictal discharges in an organotypic hippocampal slice culture model of epileptogenesis. J Clin Neurophysiol ; Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: Which animal models should be used in the search for new antiepileptic drugs?
A proposal based on experimental and clinical considerations. Epilepsy Res ;2 3: Limbic seizures produced by pilocarpine in rats: Behav Brain Res ;9 3: The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats. Exp Neurol ;97 1: Phenytoin, phenobarbital, and midazolam fail to stop status epilepticus-like activity induced by low magnesium in rat entorhinal slices, but can prevent its development.
Acta Neurol Scand ;98 3: Magnesium-free medium activates seizure-like events in the rat hippocampal slice. Brain Res ; 1: Paroxysmal epileptiform discharges in temporal lobe slices after prolonged exposure to low magnesium areresistant to clinically used anticonvulsants.
Epilepsy Res ;20 2: Neurosci Lett ; 1: The genetically epilepsy-prone rat GEPR. Ital J Neurol Sci ;16 Modelling epilepsy and seizure in developing zebrafish. Models of seizure and epilepsy. Unites states of America: Elsevier academic press; Seizures induced by pentylenetetrazole in the adult zebrafish: PLoS One ;8 1: The preclinical and therapeutic activity of the novel anticonvulsant topiramate.
CNS Drug Rev ;4 2:
MODELS OF EPILEPSY USED IN ANTIEPILEPTIC DRUG DISCOVERY: A REVIEW
Animal models for seizures and epilepsy have played a fundamental role in advancing our understanding of basic mechanisms underlying ictogenesis and. Good welfare practice in modeling seizures and epilepsy 5. Ethics in the Use of Animal Models of Seizures and Epilepsy 6. Regulatory aspects of drug. Purchase Models of Seizures and Epilepsy - 1st Edition. Print Book The first comprehensive description of animal models of epilepsy since the early 's.