Furosemide and Mannitol Suppression of Epileptic Activity in the Human Brain

2005 ◽  
Vol 94 (2) ◽  
pp. 907-918 ◽  
Author(s):  
Michael M. Haglund ◽  
Daryl W. Hochman
Keyword(s):  
Electrical Stimulation ◽  
Human Brain ◽  
Optical Imaging ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Intractable Epilepsy ◽  
Mesial Temporal Lobe Epilepsy ◽  
Epileptic Activity ◽  
Imaging Data ◽  
Epileptiform Discharges

Most research on basic mechanisms of epilepsy and the design of new antiepileptic drugs has focused on synaptic transmission or action potential generation. However, a number of laboratory studies have suggested that nonsynaptic mechanisms, such as modulation of electric field interactions via the extracellular space (ECS), might also contribute to neuronal hypersynchrony and epileptogenicity. To date, a role for nonsynaptic modulation of epileptic activity in the human brain has not been investigated. Here we studied the effects of molecules that modulate the volume and water content of the ECS on epileptic activity in patients suffering from neocortical and mesial temporal lobe epilepsy. Electrophysiological and optical imaging data were acquired from the exposed cortices of anesthetized patients undergoing surgical treatment for intractable epilepsy. Patients were given a single intravenous injection containing either 20 mg furosemide (a cation-chloride cotransporter antagonist) or 50 g mannitol (an osmolyte). Furosemide and mannitol both significantly suppressed spontaneous epileptic spikes and electrical stimulation-evoked epileptiform discharges in all subjects, completely blocking all epileptic activity in some patients without suppressing normal electroencephalographic activity. Optical imaging suggested that the spread of electrical stimulation-evoked activity over the cortex was significantly reduced by these treatments, but the magnitude of neuronal activation near the stimulating electrode was not diminished. These results suggest that nonsynaptic mechanisms play a critical role in modulating the epileptogenicity of the human brain. Furosemide and other drugs that modulate the ECS might possess clinically useful antiepileptic properties, while avoiding the side effects associated with the suppression of neuronal excitability.

scholarly journals Pannexin-1 Deficiency Decreases Epileptic Activity in Mice

2020 ◽  
Vol 21 (20) ◽  
pp. 7510 ◽  
Author(s):  
Mark S. Aquilino ◽  
Paige Whyte-Fagundes ◽  
Mark K. Lukewich ◽  
Liang Zhang ◽  
Berj L. Bardakjian ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Critical Role ◽  
Epileptic Activity ◽  
Channel Blockers ◽  
Systemic Injection ◽  
Pannexin 1 ◽  
Severe Stage ◽  
Frequency Coupling ◽  
Epilepsy Models ◽  
Cross Frequency Coupling

Objective: Pannexin-1 (Panx1) is suspected of having a critical role in modulating neuronal excitability and acute neurological insults. Herein, we assess the changes in behavioral and electrophysiological markers of excitability associated with Panx1 via three distinct models of epilepsy. Methods Control and Panx1 knockout C57Bl/6 mice of both sexes were monitored for their behavioral and electrographic responses to seizure-generating stimuli in three epilepsy models—(1) systemic injection of pentylenetetrazol, (2) acute electrical kindling of the hippocampus and (3) neocortical slice exposure to 4-aminopyridine. Phase-amplitude cross-frequency coupling was used to assess changes in an epileptogenic state resulting from Panx1 deletion. Results: Seizure activity was suppressed in Panx1 knockouts and by application of Panx1 channel blockers, Brilliant Blue-FCF and probenecid, across all epilepsy models. In response to pentylenetetrazol, WT mice spent a greater proportion of time experiencing severe (stage 6) seizures as compared to Panx1-deficient mice. Following electrical stimulation of the hippocampal CA3 region, Panx1 knockouts had significantly shorter evoked afterdischarges and were resistant to kindling. In response to 4-aminopyridine, neocortical field recordings in slices of Panx1 knockout mice showed reduced instances of electrographic seizure-like events. Cross-frequency coupling analysis of these field potentials highlighted a reduced coupling of excitatory delta–gamma and delta-HF rhythms in the Panx1 knockout. Significance: These results suggest that Panx1 plays a pivotal role in maintaining neuronal hyperexcitability in epilepsy models and that genetic or pharmacological targeting of Panx1 has anti-convulsant effects.

scholarly journals Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Guangjun Zhao ◽  
Xuchu Wang ◽  
Yanmin Niu ◽  
Liwen Tan ◽  
Shao-Xiang Zhang
Keyword(s):  
High Resolution ◽  
Human Brain ◽  
Critical Role ◽  
Feature Representation ◽  
Imaging Data ◽  
Anatomical Structures ◽  
Stacked Autoencoder ◽  
Chinese Visible Human ◽  
Visible Human ◽  
Brain Tissues

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

Synaptic Regulation of the Slow Ca2+-Activated K+ Current in Hippocampal CA1 Pyramidal Neurons: Implication in Epileptogenesis

2001 ◽  
Vol 86 (6) ◽  
pp. 2878-2886 ◽  
Author(s):  
Eduardo D. Martín ◽  
Alfonso Araque ◽  
Washington Buño
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Epileptiform Activity ◽  
Critical Role ◽  
Hippocampal Slices ◽  
Synaptic Activity ◽  
Cooperative Action ◽  
Epileptiform Discharges ◽  
Group I

The slow Ca2+-activated K+ current (sIAHP) plays a critical role in regulating neuronal excitability, but its modulation during abnormal bursting activity, as in epilepsy, is unknown. Because synaptic transmission is enhanced during epilepsy, we investigated the synaptically mediated regulation of the sIAHP and its control of neuronal excitability during epileptiform activity induced by 4-aminopyridine (4AP) or 4AP+Mg2+-free treatment in rat hippocampal slices. We used electrophysiological and photometric Ca2+ techniques to analyze the sIAHP modifications that parallel epileptiform activity. Epileptiform activity was characterized by slow, repetitive, spontaneous depolarizations and action potential bursts and was associated with increased frequency and amplitude of spontaneous excitatory postsynaptic currents and a reduced sIAHP. The metabotropic glutamate receptor (mGluR) antagonist (S)-α-methyl-4-carboxyphenylglycine did not modify synaptic activity enhancement but did prevent sIAHP inhibition and epileptiform discharges. The mGluR-dependent regulation of the sIAHP was not caused by modulated intracellular Ca2+ signaling. Histamine, isoproterenol, and (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid reduced the sIAHP but did not increase synaptic activity and failed to evoke epileptiform activity. We conclude that 4AP or 4AP+Mg-free–induced enhancement of synaptic activity reduced the sIAHP via activation of postsynaptic group I/II mGluRs. The increased excitability caused by the lack of negative feedback provided by the sIAHP contributes to epileptiform activity, which requires the cooperative action of increased synaptic activity.

scholarly journals Interaction of Sodium Valproate With Low-Frequency Electrical Stimulation During Kindlingn

2020 ◽  
Vol 11 (6) ◽  
pp. 831-840
Author(s):  
Raha Zalkhani ◽  
◽  
Ahmad Ali Moazedi ◽  
Zohreh Ghotbeddin ◽  
Mahdi Pourmahdi Borujeni ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Sodium Valproate ◽  
Wistar Rats ◽  
Critical Role ◽  
Low Frequency ◽  
Epileptic Activity ◽  
Fourth Stage ◽  
Maximum Duration ◽  
Male Wistar Rats ◽  
Stimulation Of

Introduction: The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling. Methods: One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling. Results: Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation. Conclusion: It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate.

A Functional Connection Between Inferior Frontal Gyrus and Orofacial Motor Cortex in Human

2004 ◽  
Vol 92 (2) ◽  
pp. 1153-1164 ◽  
Author(s):  
Jeremy D. W. Greenlee ◽  
Hiroyuki Oya ◽  
Hiroto Kawasaki ◽  
Igor O. Volkov ◽  
Olaf P. Kaufman ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Human Subjects ◽  
Inferior Frontal Gyrus ◽  
Critical Role ◽  
Intractable Epilepsy ◽  
Functional Connection ◽  
Corticocortical Connections ◽  
Stimulation Of

The inferior frontal gyrus (IFG) of humans is known to play a critical role in speech production. The IFG is a highly convoluted and cytoarchitectonically diverse structure, classically forming 3 subgyri. It is reasonable to speculate that during speaking the IFG, or some portion of it, influences by corticocortical connections the orofacial representational area of primary motor cortex. To test the hypothesis that such corticocortical connections exist, electrical-stimulation tract tracing experiments were performed intraoperatively on 14 human subjects undergoing surgical treatment of medically intractable epilepsy. Bipolar electrical stimulation was applied to sites on the IFG, while the resulting evoked potentials were recorded from orofacial motor cortex, using a multichannel recording array. Stimulation of the IFG evoked polyphasic waveforms on motor cortex of both language-dominant and -nondominant hemispheres. The evoked waveforms had consistent features across subjects. The responses were seen in discrete regions on precentral cortex. Stimulation of motor cortex also evoked responses on portions of IFG. The data provide evidence for a functional connection between the human IFG and orofacial motor cortex.

scholarly journals PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jingliang Zhang ◽  
Chenyu Zhang ◽  
Xiaoling Chen ◽  
Bingwei Wang ◽  
Weining Ma ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neuronal Excitability ◽  
Granule Cells ◽  
Critical Role ◽  
Intrinsic Excitability ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Potential Therapeutic Target ◽  
Seizure Model

AbstractTemporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE.

scholarly journals Magnetic source imaging for the surgical evaluation of electroencephalography-confirmed secondary bilateral synchrony in intractable epilepsy

2009 ◽  
Vol 111 (6) ◽  
pp. 1248-1256 ◽  
Author(s):  
Edward F. Chang ◽  
Srikantan S. Nagarajan ◽  
Mary Mantle ◽  
Nicholas M. Barbaro ◽  
Heidi E. Kirsch
Keyword(s):  
Mr Imaging ◽  
Intractable Epilepsy ◽  
Focal Lesion ◽  
Seizure Type ◽  
Source Imaging ◽  
Magnetic Source Imaging ◽  
Ms Imaging ◽  
Epileptiform Discharges ◽  
Magnetic Source ◽  
Imaging Results

Object Routine scalp electroencephalography (EEG) cannot always distinguish whether generalized epileptiform discharges are the result of primary bilateral synchrony or secondary bilateral synchrony (SBS) from a focal origin; this is an important distinction because the latter may be amenable to resection. Whole-head magnetoencephalography (MEG) has superior spatial resolution compared with traditional EEG, and can potentially elucidate seizure foci in challenging epilepsy cases in which patients are undergoing evaluation for surgery. Methods Sixteen patients with medically intractable epilepsy in whom SBS was suspected were referred for magnetic source (MS) imaging. All patients had bilateral, synchronous, widespread, and most often generalized spike-wave discharges on scalp EEG studies, plus some other clinical (for example, seizure semiology) or MR imaging feature (for example, focal lesion) suggesting focal onset and hence possible surgical candidacy. The MS imaging modality is the combination of whole-head MEG and parametric reconstruction of corresponding electrical brain sources. An MEG and simultaneous EEG studies were recorded with a 275-channel whole-head system. Single-equivalent current dipoles were estimated from the MEG data, and dipole locations and orientations were superimposed on patients' MR images. Results The MS imaging studies revealed focal dipole clusters in 12 (75%) of the 16 patients, of which a single dipole cluster was identified in 7 patients (44%). Patient age, seizure type, duration of disease, video-EEG telemetry, and MR imaging results were analyzed to determine factors predictive of having clusters revealed on MS imaging. Of these factors, only focal MR imaging anatomical abnormalities were associated with dipole clusters (chi-square test, p = 0.03). Selective resections (including the dipole cluster) in 7 (87%) of 8 patients resulted in seizure-free or rare seizure outcomes (Engel Classes I and II). Conclusions Magnetic source imaging may provide noninvasive anatomical and neurophysiological confirmation of localization in patients in whom there is a suspicion of SBS (based on clinical or MR imaging data), especially in those with an anatomical lesion. Identification of a focal seizure origin has significant implications for both resective and nonresective treatment of intractable epilepsy.

A Novel Real-Time Thermal Analysis and Layer Time Control Framework for Large Scale Additive Manufacturing

2020 ◽  
Author(s):  
Sepehr Fathizadan ◽  
Feng Ju ◽  
Kyle Rowe ◽  
Alex Fiechter ◽  
Nils Hofmann
Keyword(s):  
Additive Manufacturing ◽  
Surface Temperature ◽  
Real Time ◽  
Large Scale ◽  
Production Efficiency ◽  
Control Method ◽  
Data Extraction ◽  
Critical Role ◽  
Imaging Data ◽  
Time Data

Abstract Production efficiency and product quality need to be addressed simultaneously to ensure the reliability of large scale additive manufacturing. Specifically, print surface temperature plays a critical role in determining the quality characteristics of the product. Moreover, heat transfer via conduction as a result of spatial correlation between locations on the surface of large and complex geometries necessitates the employment of more robust methodologies to extract and monitor the data. In this paper, we propose a framework for real-time data extraction from thermal images as well as a novel method for controlling layer time during the printing process. A FLIR™ thermal camera captures and stores the stream of images from the print surface temperature while the Thermwood Large Scale Additive Manufacturing (LSAM™) machine is printing components. A set of digital image processing tasks were performed to extract the thermal data. Separate regression models based on real-time thermal imaging data are built on each location on the surface to predict the associated temperatures. Subsequently, a control method is proposed to find the best time for printing the next layer given the predictions. Finally, several scenarios based on the cooling dynamics of surface structure were defined and analyzed, and the results were compared to the current fixed layer time policy. It was concluded that the proposed method can significantly increase the efficiency by reducing the overall printing time while preserving the quality.

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