scholarly journals D-serine mitigates cell loss associated with temporal lobe epilepsy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephen Beesley ◽  
Thomas Sullenberger ◽  
Kathryn Crotty ◽  
Roshan Ailani ◽  
Cameron D’Orio ◽  
...  
Keyword(s):  
Amino Acid ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Therapeutic Agent ◽  
Neuronal Loss ◽  
Cell Loss ◽  
Unknown Etiology ◽  
Entorhinal Area ◽  
Drug Resistant Epilepsy ◽  
The Brain

Abstract Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults, with an unknown etiology. A hallmark of TLE is the characteristic loss of layer 3 neurons in the medial entorhinal area (MEA) that underlies seizure development. One approach to intervention is preventing loss of these neurons through better understanding of underlying pathophysiological mechanisms. Here, we show that both neurons and glia together give rise to the pathology that is mitigated by the amino acid D-serine whose levels are potentially diminished under epileptic conditions. Focal administration of D-serine to the MEA attenuates neuronal loss in this region thereby preventing epileptogenesis in an animal model of TLE. Additionally, treatment with D-serine reduces astrocyte counts in the MEA, alters their reactive status, and attenuates proliferation and/or infiltration of microglia to the region thereby curtailing the deleterious consequences of neuroinflammation. Given the paucity of compounds that reduce hyperexcitability and neuron loss, have anti-inflammatory properties, and are well tolerated by the brain, D-serine, an endogenous amino acid, offers new hope as a therapeutic agent for refractory TLE.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

scholarly journals Magnetic resonance spectroscopy of the brain in the diagnosis of temporal lobe epilepsy

2018 ◽  
Vol 10 (1S) ◽  
pp. 51-55
Author(s):  
E. S. Solomatova ◽  
N. A. Shnaider ◽  
A. A. Molgachev ◽  
D. V. Dmitrenko ◽  
I. G. Strotskaya
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
English Language ◽  
Russian Language ◽  
Resonance Spectroscopy ◽  
Epileptogenic Focus ◽  
Patients With Epilepsy ◽  
The Brain

The temporal lobe is the most epileptogenic region of the brain. 90% of patients with temporal ictal epileptomorphic EEG activity have a variable long history of seizures. Magnetic resonance spectroscopy  (MRS) may be useful in identifying an epileptogenic focus in patients  with epilepsy without apparent structural pathology at neuroimaging.Objective: to systematize the results of early studies on this issue.Materials and methods. An electronic search was carried out in two English-language (Medline, PubMed) and one Russian-language (eLIBRARY.RU) databases. The search queries found  18,019 citations, by which 12 full-text articles were selected.Results and discussion. The main criteria for the diagnosis of temporal lobe epilepsy by MRS is to lower the level of N-acetylaspartate (NAA), the ratio of NAA to creatinine + choline  (NAA/(Cr + Cho) in the brain region where there is neuronal death  or damage, as well as a change in the level of myo-inositol, the  elevated level of which indicates the presence of an epileptogenic  focus, while the decreased one shows the spread of pathological activity to the adjacent tissues.Conclusion. This review will contribute to a better diagnosis of temporal lobe epilepsy, as well as to the intravital noninvasive detection of metabolic changes in the brain long before the development of structural pathology.

scholarly journals Recent developments in cognitive fMRI for temporal lobe epilepsy

2019 ◽  
Vol 33 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Victor Schmidbauer ◽  
Silvia Bonelli
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Visual Memory ◽  
Imaging Modality ◽  
Memory Function ◽  
Brain Regions ◽  
Epileptogenic Zone ◽  
Brain Areas ◽  
Recent Developments ◽  
The Brain

AbstractEpilepsy is frequently accompanied by severe cognitive side effects. Temporal lobe epilepsy (TLE), and even successful surgical treatment, may affect cognitive function, in particular language as well as verbal and visual memory function. Epilepsy arising from the temporal lobe can be controlled surgically in up to 70% of patients. The goals of epilepsy surgery are to remove the brain areas generating the seizures without causing or aggravating neuropsychological deficits. This requires accurate localization of the brain areas generating the seizures (“epileptogenic zone”) and the areas responsible for motor and cognitive functions, such as language and memory (“essential brain regions”) during presurgical evaluation. In the past decades, functional magnetic resonance imaging (fMRI) has been increasingly used to noninvasively lateralize and localize not only primary motor and somatosensory areas, but also brain areas that are involved in everyday language and memory processes. The imaging modality also shows potential for predicting the effects of temporal lobe resection on language and memory function. Together with other MRI modalities, cognitive fMRI is a promising tool to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared.The aim of this review is to provide an overview of recent developments and practical recommendations for the clinical use of cognitive fMRI in TLE.

Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy

1994 ◽  
Vol 36 (6) ◽  
pp. 925-927 ◽  
Author(s):  
Thomas R. Henry ◽  
Thomas L. Babb ◽  
Jerome Engel ◽  
John C. Mazziotta ◽  
Michael E. Phelps ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Neuronal Loss

Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and a histopathological analysis

2004 ◽  
Vol 101 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Aaron A. Cohen-Gadol ◽  
Jullie W. Pan ◽  
Jung H. Kim ◽  
Dennis D. Spencer ◽  
Hoby H. Hetherington
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mr Spectroscopy ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Mesial Temporal Lobe Epilepsy ◽  
Content Type ◽  
Neuronal Cell Loss ◽  
Gfap Immunoreactivity ◽  
Fine Print

Object. Proton magnetic resonance (MR) spectroscopy imaging of the ratio of N-acetylaspartate (NAA) to creatine (Cr) has proved efficacious as a localizing tool in demonstrating the metabolic changes associated with temporal lobe epilepsy. To analyze the significance of these MR spectroscopy findings further, the authors explored the relationship between regional alterations in the NAA/Cr ratio in hippocampi measured preoperatively and histopathological findings in hippocampi resected in patients with intractable mesial temporal lobe epilepsy (MTLE). Methods. Twelve patients in whom the diagnosis of MTLE had been made and 12 healthy volunteers with no known history of neurological disease underwent high-resolution 1H MR spectroscopy imaging of NAA and Cr (0.64 cm3 nominal voxel resolution) in five voxels spanning the anteroposterior length of the hippocampus. The authors correlated the NAA/Cr ratio with neuropathological findings in resected hippocampi, specifically glial fibrillary acidic protein (GFAP) immunoreactivity and pyramidal neuronal loss. A linear regression analysis of the ipsilateral NAA/Cr ratio revealed a statistically significant relation to the extent of hippocampal neuronal loss in only the CA2 sector (correlation coefficient [r] = −0.66, p < 0.03). The ipsilateral NAA/Cr ratio displayed significant regressions with GFAP immunoreactivity from all the CA sectors (r values ranged from −0.69 and p < 0.01 for the CA4 sector to −0.88 and p < 0.001 for the CA2 sector) except for the CA1. The extent of neuronal cell loss in every hippocampal subfield (r = 0.71−0.74, p < 0.007), except the CA2 (p = 0.08), correlated to the extent of neuronal cell loss in the dentate gyrus. There was no significant relationship between the duration or frequency of seizures and the mean ipsilateral NAA/Cr ratio; however, the mean density of GFAP-immunopositive cells correlated with seizure frequency (p < 0.03). Conclusions. The NAA/Cr ratio may not measure the full extent of hippocampal neuronal cell loss. The significant association of the NAA/Cr ratio with the GFAP immunoreactivity of most CA sectors indicates that the NAA/Cr ratio may provide a more accurate measurement of recent neuronal injury caused by epileptic activity. The coupling between neuronal impairment and astroglial GFAP expression may indicate the close association between neuronal and glial dysfunction in patients with epilepsy.

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy

2017 ◽  
Vol 76 ◽  
pp. 168-177 ◽  
Author(s):  
Marino Muxfeldt Bianchin ◽  
Tonicarlo Rodrigues Velasco ◽  
Lauro Wichert-Ana ◽  
Antonio Carlos dos Santos ◽  
Américo Ceiki Sakamoto
Keyword(s):  
Surgical Treatment ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mesial Temporal Lobe Epilepsy ◽  
Drug Resistant ◽  
Mesial Temporal Lobe ◽  
Drug Resistant Epilepsy

scholarly journals The Default Mode Network In Patient with Temporal Lobe Epilepsy (TLE): A Resting State fMRI Study

2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Shuhada J.M ◽  
Husbani M.A.R ◽  
A I A Hamid ◽  
Muhammad
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Default Mode Network ◽  
Resting State ◽  
Healthy Subjects ◽  
Brain Activation ◽  
Resting State Fmri ◽  
Default Mode ◽  
Parietal Lobes ◽  
The Brain

The default mode network (DMN) is involved in conscious, resting state cognition and is thought to be affected in TLE where seizures cause impairment of consciousness. The study aimed to evaluate the brain activation of the DMN regions in both temporal lobe epilepsy (TLE) patients  and healthy subjects by using resting-state functional Magnetic Resonance Imaging (rsfMRI) technique. A same number of fourteen participants with age and gender matched for the healthy subjects and TLE patients were selected with the average age is 36.9 and 37.0 years old, respectively. The rsfMRI imaging protocol was executed using a 3-T Phillips Achieva MRI scanner at the Radiology Department, Hospital Universiti Sains Malaysia (HUSM). For healthy subjects, the brain activation cluster in bilateral superior parietal lobes (SPL),precuneus (PRE), supramarginal gyrus (SMG) and inferior parietal lobes (IPL) were found higher than TLE patients. While for TLE patients displays higher activation clusters in bilateral MFG, STG, and ANG. The result from  random effects (RFX) on  two-sample t-tests thresholded at p = 0.001 revealed that the TLE patients display significantly higher activations on the bilateral superior frontal gyrus (SFG), left SMG, left middle frontal gyrus (MFG) and right IPL. However for the core-region of DMN such as  bilateral precuneus, left MFG, bilateral STG and bilateral IPL were significantly activated but the number of voxels survives are substantially smaller than other regions such as bilateral SFG. The findings suggested that TLE patients may suffer from an impairment in some DMN region, which may cause certain neuropsychological and cognitive degradation.       Keywords: resting-state fMRI, temporal lobe epilepsy, brain activation, two-sample t-tests

scholarly journals Systemic evidence of acute seizure-associated neuronal injury in patients with temporal lobe epilepsy

2017 ◽  
Author(s):  
Shailaja Kunda ◽  
Reghann G LaFrance-Corey ◽  
Fatemeh Khadjevand ◽  
Gregory A Worrell ◽  
Charles L Howe
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Neuron Specific Enolase ◽  
Neuronal Loss ◽  
Neuronal Injury ◽  
Serum Levels ◽  
Large Signal ◽  
Acute Seizure ◽  
Neuroprotective Strategies ◽  
Glial Injury

AbstractPatients with drug refractory temporal lobe epilepsy frequently accumulate cognitive impairment over time, suggesting neuronal loss induced by seizures. We measured serum levels of neuron-specific enolase (NSE), a neuronal injury marker, relative to levels of S100β, a marker of glial injury, at 6 AM, 9 AM, noon, 3 PM, and 6 PM over the course of several days in 7 epilepsy patients and 4 healthy controls. All epilepsy patients exhibited significant deviations in NSE levels through time, and 4 of the epilepsy patients exhibited large sample entropy values and large signal variation metrics for NSE relative to S100β. Controls did not exhibit such changes. Correlation analysis revealed that NSE levels were significantly elevated after clinical seizure events. There was also a highly significant relationship between increased EEG spike frequency and an increase in serum NSE levels measured 24 hours later. The detection of large but transient post-ictal increases in NSE suggests that even self-limited seizures may cause an injury to neurons that underlies cognitive decline in some patients. Post-ictal assessment of serum NSE may serve as a biomarker for measuring the efficacy of future acute neuroprotective strategies in epilepsy patients.

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