scholarly journals T-channels: Short-Term Up-Regulation Causes Long-Term Consequences in Epilepsy

2009 ◽  
Vol 9 (4) ◽  
pp. 121-123
Author(s):  
Nicholas P. Poolos

Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy. Becker AJ, Pitsch J, Sochivko D, Opitz T, Staniek M, Chen CC, Campbell KP, Schoch S, Yaari Y, Beck H. J Neurosci 2008 Dec 3;28(49):13341–13353. In both humans and animals, an insult to the brain can lead, after a variable latent period, to the appearance of spontaneous epileptic seizures that persist for life. The underlying processes, collectively referred to as epileptogenesis, include multiple structural and functional neuronal alterations. We have identified the T-type Ca2+ channel Cav3.2 as a central player in epileptogenesis. We show that a transient and selective upregulation of Cav3.2 subunits on the mRNA and protein levels after status epilepticus causes an increase in cellular T-type Ca2+ currents and a transitional increase in intrinsic burst firing. These functional changes are absent in mice lacking Cav3.2 subunits. Intriguingly, the development of neuropathological hallmarks of chronic epilepsy, such as subfield-specific neuron loss in the hippocampal formation and mossy fiber sprouting, was virtually completely absent in Cav3.2- /– mice. In addition, the appearance of spontaneous seizures was dramatically reduced in these mice. Together, these data establish transcriptional induction of Cav3.2 as a critical step in epileptogenesis and neuronal vulnerability.

Kardiologiia ◽  
2021 ◽  
Vol 60 (12) ◽  
pp. 90-96
Author(s):  
S. E. Serdyuk ◽  
K. V. Davtyan ◽  
S. G. Burd ◽  
E. S. Mishina ◽  
O. M. Drapkina ◽  
...  

Aim      To determine the type and incidence of ictal bradyarrhythmias in patients with drug-resistant types of epilepsy by long-term electrocardiogram (ECG) monitoring.Material and methods  Subcutaneous ECG monitors programed for recording pauses >3 sec and episodes of bradycardia ≤45 bpm were implanted in 193 patients with persistent epileptic seizures without organic pathology of the myocardium. Recording was activated by the patient/family at the onset of epileptic seizure. The follow-up period was 36 months with visits to the clinic every three months.Results For 36 months of monitoring, 6494 ECG fragments were recorded. Ictal bradycardia was observed in 6.7 % of patients, including ictal asystole in 2.6 % of patients. Episodes of bradycardia and asystole during epileptic seizures were transient and developed significantly more frequently in men, patients with long duration of the disease, bilateral tonic-clonic or focal seizures with disorder of consciousness, during sleep, on the background of treatment with several antiepileptic agents, mostly from the group of potassium channel blockers.Conclusion      Bradyarrhythmias accompanying epileptic seizures are transient and reproducible from seizure to seizure. They reflect functional changes in the myocardium and do not determine the life prediction for patients with epilepsy without organic pathology of the heart.


2008 ◽  
Vol 66 (4) ◽  
pp. 853-860 ◽  
Author(s):  
Yaima del Carmen Garrido Sanabria ◽  
Gustavo Adolfo Argañaraz ◽  
Eliangela Lima ◽  
Margareth Rose Priel ◽  
Edvaldo da Silva Trindade ◽  
...  

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.


2005 ◽  
Vol 93 (1) ◽  
pp. 316-336 ◽  
Author(s):  
Bin Hu ◽  
Sergei Karnup ◽  
Lei Zhou ◽  
Armin Stelzer

Memory impairment is a common consequence of epileptic seizures. The hippocampal formation is particularly prone to seizure-induced amnesia due to its prominent role in mnemonic processes. We used the isolated CA1 slice preparation to examine effects of seizure-like activity on hippocampal plasticity, long-term potentiation (LTP), and long-term depression (LTD). Repeated spontaneous ictal events, generated in the presence of antagonists of GABAA receptor function, led to a stepwise erasure of LTP (termed spontaneous depotentiation, SDP). SDP could be initiated at various stages of LTP consolidation (tested ≤120 min after the induction of LTP). Renewed tetanic stimulation re-established LTP. SDP was remarkably specific: baseline transmission and other forms of hippocampal plasticity, i.e., Ca2+-induced LTP and two forms of LTD [(RS)-3,5-dihydroxyphenyglycine (DHPG) mediated and low-frequency stimulation mediated] were not affected by the same type of seizure activity. SDP was blocked in the presence of the group I mGluR antagonist ( S)-4-carboxyphenylglycine. The mGluR1 antagonist ( S)-(+)-α-amino-methylbenzeneacetic acid blocked ∼80%, the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)-pyridine ∼30% of SDP. Most efficient implementation of SDP was observed during seizures in the combined presence of the group I mGluR agonist DHPG and the GABAA antagonist bicuculline. However, similar ictal activity generated in the presence of DHPG alone did not lead to SDP in the vast majority of recordings. Complete disinhibition and at least partial activation of group I mGluR were necessary conditions for the induction of SDP. The depotentiating pharmacological conditions were accompanied by tonic membrane depolarization of CA1 pyramidal cells. Since hyperpolarization (by negative current injection) prevented intracellular SDP under depotentiating pharmacological conditions and depolarization (by positive current injection) led to selective intracellular SDP in the non-depotentiating seizure protocol of DHPG, it is concluded that cell depolarization was a sufficient condition for seizure-like activity to reverse hippocampal LTP.


Epilepsia ◽  
2003 ◽  
Vol 44 (7) ◽  
pp. 893-903 ◽  
Author(s):  
Véronique André ◽  
Marie-Aude Rigoulot ◽  
Estelle Koning ◽  
Arielle Ferrandon ◽  
Astrid Nehlig

GeroPsych ◽  
2013 ◽  
Vol 26 (3) ◽  
pp. 185-199 ◽  
Author(s):  
Christina Röcke ◽  
Annette Brose

Whereas subjective well-being remains relatively stable across adulthood, emotional experiences show remarkable short-term variability, with younger and older adults differing in both amount and correlates. Repeatedly assessed affect data captures both the dynamics and stability as well as stabilization that may indicate emotion-regulatory processes. The article reviews (1) research approaches to intraindividual affect variability, (2) functional implications of affect variability, and (3) age differences in affect variability. Based on this review, we discuss how the broader literature on emotional aging can be better integrated with theories and concepts of intraindividual affect variability by using appropriate methodological approaches. Finally, we show how a better understanding of affect variability and its underlying processes could contribute to the long-term stabilization of well-being in old age.


GYNECOLOGY ◽  
2020 ◽  
Vol 21 (6) ◽  
pp. 12-15
Author(s):  
Elena V. Tsallagova ◽  
Vasily O. Generalov ◽  
Timur R. Sadykov

Pregnancy is the most dangerous period in terms of interruption of even persistent and long-term remission. At the same time increasing the dose of anticonvulsant increases the risk of teratogenic effects. Aim. to assess the possibility of using progesterone to prevent relapse of epileptic seizures during pregnancy. Materials and methods. 38 pregnant patients with epilepsy with clinical remission before pregnancy, with relapse of epileptic seizures in I trimester of pregnancy, age 31.81.4 years. Dydrogesterone in a dose of 10 to 60 mg/day was prescribed after the relapse of remission. Anticonvulsant dosage was not changed. The blood progesterone concentration and EEG control was carried out. Results. During pregnancy, the level of progesterone in the blood gradually increased from 77.8 nmol/l at 78 weeks of pregnancy to 521.1 nmol/l at 3637 weeks of pregnancy, without exceeding the limits. EEG results did not deteriorate. None of the patients had seizures during pregnancy. Conclusion. Progesterone therapy is an adequate and safe alternative to increasing the dose of anticonvulsants in case of recurrent seizures during pregnancy.


2019 ◽  
Author(s):  
Svetlana Serdyuk ◽  
Karapet V. Davtyan ◽  
Sergey G. Burd ◽  
Oksana M. Drapkina ◽  
Sergey A. Boytsov ◽  
...  

2019 ◽  
Vol 16 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Hadas Han ◽  
Sara Eyal ◽  
Emma Portnoy ◽  
Aniv Mann ◽  
Miriam Shmuel ◽  
...  

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.


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