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Barbara Pijet, Marzena Stefaniuk, Agnieszka Kostrzewska-Ksiezyk, Photini-Effie Tsilibary, Athina Tzinia, Leszek Kaczmarek
Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that often develops secondary to traumatic brain injury (TBI) that is caused by an external mechanical force. Recent evidence shows that the brain extracellular matrix plays a major role in the remodeling of neuronal connections after injury. One of the proteases that is presumably responsible for this process is matrix metalloproteinase-9 (MMP-9). The levels of MMP-9 are elevated in rodent brain tissue and human blood samples after TBI. However, no studies have described the influence of MMP-9 on the development of PTE...
April 17, 2018: Molecular Neurobiology
Ramsha Iqbal, Gaurav K Jain, Fouzia Siraj, Divya Vohora
Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABAA receptor modulating neurosteroid...
April 9, 2018: Epilepsy Research
Evy Cleeren, Cindy Casteels, Karolien Goffin, Michel Koole, Koen Van Laere, Peter Janssen, Wim Van Paesschen
OBJECTIVE: We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis. METHODS: Because it is rarely possible to study epileptogenesis in humans, we applied the electrical amygdala kindling model in nonhuman primates to image longitudinal changes in type 1 cannabinoid receptor (CB1R) binding and cerebral glucose metabolism. Two rhesus monkeys received [18 F]-MK-9470 and fluorodeoxyglucose-positron emission tomography ([18 F]-FDG -PET) scans in each of the 4 kindling stages to quantify relative changes over time of CB1R binding and cerebral glucose metabolism in vivo...
April 17, 2018: Epilepsia
Jana Tchekalarova, Dimitrinka Atanasova, Lidia Kortenska, Milena Atanasova, Nikolai Lazarov
Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and maintained for a period of 10 weeks in Wistar rats...
April 10, 2018: Neurobiology of Disease
Ursula Geronzi, Federica Lotti, Salvatore Grosso
The brain is particularly susceptible to oxidative stress being the most aerobically active organ in the body due to its high metabolic demands. There is evidence that neuronal hyperexcitability and oxidative injury produced by an excessive production of free radicals may play a role in the initiation and progression of epilepsy. Understanding the role of oxidative stress in epileptogenesis is essential to delineate appropriate therapeutic strategies. Neuroprotectant or antioxidant compounds may exert positive effects when associated with antiepileptic drugs (AEDs)...
April 13, 2018: Expert Review of Neurotherapeutics
Alison Pack
No abstract text is available yet for this article.
March 2018: Epilepsy Currents
Jerome Engel
Epilepsy is one of the most common brain disorders, causing serious disability and premature death worldwide. Approximately 1.2% of the U.S. population has active epilepsy, and 30 to 40% have seizures that do not respond to antiseizure drugs. There currently is no treatment available that prevents epilepsy following a potential epileptogenic insult, and the search for disease or syndrome modifying interventions for epilepsy is a high priority of neurobiological research. This requires better understanding of neuronal mechanisms underlying the development of epilepsy, and biomarkers of this process that would permit cost-effective drug discovery, and validation in clinical trials, for potential antiepileptogenic compounds...
April 3, 2018: Neurobiology of Disease
Fanny Demars, Kristen Clark, Megan S Wyeth, Emily Abrams, Paul S Buckmaster
Harmful blooms of domoic acid (DA)-producing algae are a problem in oceans worldwide. DA is a potent glutamate receptor agonist that can cause status epilepticus and in survivors, temporal lobe epilepsy. In mice, one-time low-dose in utero exposure to DA was reported to cause hippocampal damage and epileptiform activity, leading to the hypothesis that unrecognized exposure to DA from contaminated seafood in pregnant women can damage the fetal hippocampus and initiate temporal lobe epileptogenesis. However, development of epilepsy (i...
April 3, 2018: Neurotoxicology
Karine Yu Sarkisova, Alla V Gabova
WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression-like symptoms and spontaneous generalized spike-wave discharges (SWDs) in the EEG at the age of 6-8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression-like comorbidity later in life. To achieve this, a cross-fostering procedure was used...
March 31, 2018: Genes, Brain, and Behavior
Toshimitsu Hiragi, Yuji Ikegaya, Ryuta Koyama
Microglia are the resident immune cells in the brain that constitute the brain's innate immune system. Recent studies have revealed various functions of microglia in the development and maintenance of the central nervous system (CNS) in both health and disease. However, the role of microglia in epilepsy remains largely undiscovered, partly because of the complex phenotypes of activated microglia. Activated microglia likely exert different effects on brain function depending on the phase of epileptogenesis. In this review, we mainly focus on the animal models of temporal lobe epilepsy (TLE) and discuss the proepileptic and antiepileptic roles of activated microglia in the epileptic brain...
March 28, 2018: Cells
Brenda Marrero-Rosado, Franco Rossetti, Matthew W Rice, Mark C Moffett, Robyn Lee, Michael F Stone, Lucille A Lumley
Elderly individuals compose a large percentage of the world population; however, few studies have addressed the efficacy of current medical countermeasures (MCM) against the effects of chemical warfare nerve agent exposure in aged populations. We evaluated the efficacy of the anticonvulsant diazepam in an old adult rat model of soman (GD) poisoning and compared the toxic effects to those observed in young adult rats when anticonvulsant treatment is delayed. After determining their respective median lethal dose (LD50) of GD, we exposed young adult and old adult rats to an equitoxic 1...
March 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Kenia Pardo-Peña, Ana Sánchez-Lira, Juan C Salazar-Sánchez, Alberto Morales-Villagrán
Status epilepticus (SE) can result in an overproduction of hydrogen peroxide (H2O2), which contributes to oxidative stress and brain injury during different phases of epileptogenesis and seizures. In this study, we measured the extracellular H2O2 concentration in the rat hippocampus in a temporal lobe epilepsy model. A new fluorescent technique for measuring H2O2in vivo simultaneously with electroencephalography recording was tested. The method consists of mixing microdialysate with an enzymatic reactor to produce a fluorescent compound...
March 28, 2018: Neuroreport
Yicong Lin, Yuping Wang
The revolution in theory, swift technological developments, and invention of new devices have driven tremendous progress in neurostimulation as a third-line treatment for epilepsy. Over the past decades, neurostimulation took its place in the field of epilepsy as an advanced treatment technique and opened up a new world. Numerous animal studies have proven the physical efficacy of stimulation of the brain and peripheral nerves. Based on this optimistic fundamental research, new advanced techniques are being explored in clinical practice...
December 2017: Epilepsia Open
Doodipala Samba Reddy, Ryan F Yoshimura, Gunasekaran Ramanathan, Chase Carver, Timothy B Johnstone, Derk J Hogenkamp, Kelvin W Gee
OBJECTIVE: Subunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for β2/3 -subunit containing GABA-A receptors (β2/3 -selective PAMs) that are nonbenzodiazepine site-mediated and do not show an α-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance...
March 24, 2018: Epilepsy & Behavior: E&B
K Yu Kalitin, O Yu Grechko, A A Spasov, A G Sukhov, V A Anisimova, A E Matukhno
The study examined the effect of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-α] benzimidazole dihydrochloride (RU-1205) on the latency of seizures provoked by corazol, bicuculline, or picrotoxin. This agent (10 and 20 mg/kg) increased the seizure latency in the experimental models of epileptogenesis. The blockers of GABAA and GABAA -ρ receptors picrotoxin and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, respectively, were employed to study the effects of RU-1205 on electrical activity of somatosensory cortical neurons and on formation of pathological rhythms in the rat brain...
March 27, 2018: Bulletin of Experimental Biology and Medicine
Elena Y Smirnova, Dmitry V Amakhin, Sergey L Malkin, Anton V Chizhov, Aleksey V Zaitsev
Profound alterations in both the synaptic and intrinsic membrane properties of neurons that increase the neuronal network excitability are found in epileptic tissue. However, there are still uncertainties regarding the kind of changes in the intrinsic membrane properties occuring during epileptogenesis. Epileptogenesis is typically triggered by the initial brain-damaging insult, and status epilepticus (SE) is one of such insults. In the present study, we explored the acute changes in the intrinsic membrane properties of pyramidal cells one day after SE in a rat lithium-pilocarpine model...
March 23, 2018: Neuroscience
Yasser A Khadrawy, Hussein G Sawie, Eman N Hosny
Background The present study aims to investigate the neuroprotective effect of curcumin nanoparticles (Cur-NP) on the rat model of status epilepticus (SE) induced by pilocarpine. Methods In the present study, animals were divided into three groups: control animals, rat model of SE induced by a single dose of pilocarpine (380 mg/kg) injected intraperitoneally, and rat model of SE that received a daily intraperitoneal injection of Cur-NP (50 mg/kg) for four consecutive days prior to pilocarpine administration...
March 23, 2018: Journal of Complementary & Integrative Medicine
Ying Liu, Teng Wang, Xi Liu, Yuetao Wen, Tao Xu, Xinyuan Yu, Xin Wei, Xueying Ding, Lijuan Mo, Maojia Yin, Xinjie Tan, Lifen Chen
BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFβ and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation...
March 22, 2018: Journal of Neuroinflammation
Chandra Bhushan Mishra, Shikha Kumari, Andrea Angeli, Silvia Bua, Manisha Tiwari, Claudiu T Supuran
Two series of novel benzenesulfonamide derivatives were synthesized and evaluated for their human carbonic anhydrase (CA, EC inhibitory activity against four isoforms, hCA I, hCA II, hCA VII and hCA IX. It was found that compounds of both series showed low to medium nanomolar inhibitory potential against all isoforms. Some of these derivatives displayed selective inhibition against the epileptogenesis-associated isoforms hCA II and VII, within the nanomolar range. These potent hCA II and VII inhibitors were evaluated as anticonvulsant agents against MES as well as sc-PTZ induced convulsions...
March 22, 2018: Journal of Medicinal Chemistry
Mark H Myers, Robert Kozma
Simulations of EEG data provide the understanding of how the limbic system exhibits normal and abnormal states of the electrical activity of the brain. While brain activity exhibits a type of homeostasis of excitatory and inhibitory mesoscopic neuron behavior, abnormal neural firings found in the seizure state exhibits brain instability due to runaway oscillatory entrained neural behavior. We utilize a model of mesoscopic brain activity, the KIV model, where each network represents the areas of the limbic system, i...
April 2018: Cognitive Neurodynamics
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