Limbic Network Interactions Leading to Hyperexcitability in a Model of Temporal Lobe Epilepsy

2002 ◽  
Vol 87 (1) ◽  
pp. 634-639 ◽  
Author(s):  
Margherita D'Antuono ◽  
Ruba Benini ◽  
Giuseppe Biagini ◽  
Giovanna D'Arcangelo ◽  
Michaela Barbarosie ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Brain Slices ◽  
Hippocampal Damage ◽  
Functional Changes ◽  
Interictal Discharges

In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 μM) in hippocampus-EC slices from mice injected with pilocarpine 13–22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (≤6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.

scholarly journals Electrographic Features of Spontaneous Recurrent Seizures in a Mouse Model of Extended Hippocampal Kindling

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Haiyu Liu ◽  
Uilki Tufa ◽  
Anya Zahra ◽  
Jonathan Chow ◽  
Nila Sivanenthiran ◽  
...  
Keyword(s):  
Mouse Model ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Low Voltage ◽  
Brain Slices ◽  
Limbic Structure ◽  
Epileptiform Discharges ◽  
Spontaneous Recurrent Seizures

Abstract Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures (SRS) and comorbidities. Kindling through repetitive brief stimulation of a limbic structure is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling over a period up to a few months can induce SRS, which may simulate slowly evolving epileptogenesis of temporal lobe epilepsy. Currently, electroencephalographic (EEG) features of SRS in rodent models of extended kindling remain to be detailed. We explored this using a mouse model of extended hippocampal kindling. Intracranial EEG recordings were made from the kindled hippocampus and unstimulated hippocampal, neocortical, piriform, entorhinal, or thalamic area in individual mice. Spontaneous EEG discharges with concurrent low-voltage fast onsets were observed from the two corresponding areas in nearly all SRS detected, irrespective of associated motor seizures. Examined in brain slices, epileptiform discharges were induced by alkaline artificial cerebrospinal fluid in the hippocampal CA3, piriform and entorhinal cortical areas of extended kindled mice but not control mice. Together, these in vivo and in vitro observations suggest that the epileptic activity involving a macroscopic network may generate concurrent discharges in forebrain areas and initiate SRS in hippocampally kindled mice.

scholarly journals Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Deok-Sang Hwang ◽  
Hyo Geun Kim ◽  
Jun-Bock Jang ◽  
Myung Sook Oh
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Substantia Nigra Pars Compacta ◽  
Inflammatory Factors ◽  
Dopaminergic Cell ◽  
Therapeutic Implications ◽  
Anti Inflammatory ◽  
Inflammatory Action

Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in anin vitroandin vivomodel of Parkinson’s disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factorα(TNF-α), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50 mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.

scholarly journals Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

2016 ◽  
Vol 115 (6) ◽  
pp. 3229-3237 ◽  
Author(s):  
Massimo Avoli ◽  
Marco de Curtis ◽  
Vadym Gnatkovsky ◽  
Jean Gotman ◽  
Rüdiger Köhling ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Low Voltage ◽  
Mesial Temporal Lobe Epilepsy ◽  
Seizure Onset ◽  
Experimental Conditions ◽  
Eeg Recordings ◽  
Inhibitory Signaling

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.

scholarly journals Excitatory Input Onto Hilar Somatostatin Interneurons Is Increased in a Chronic Model of Epilepsy

2010 ◽  
Vol 104 (4) ◽  
pp. 2214-2223 ◽  
Author(s):  
Brian Halabisky ◽  
Isabel Parada ◽  
Paul S. Buckmaster ◽  
David A. Prince
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Fluorescent Protein ◽  
Hippocampal Slices ◽  
Inhibitory Neurons ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Whole Cell ◽  
Functional Changes

The density of somatostatin (SOM)-containing GABAergic interneurons in the hilus of the dentate gyrus is significantly decreased in both human and experimental temporal lobe epilepsy. We used the pilocarpine model of status epilepticus and temporal lobe epilepsy in mice to study anatomical and electrophysiological properties of surviving somatostatin interneurons and determine whether compensatory functional changes occur that might offset loss of other inhibitory neurons. Using standard patch-clamp techniques and pipettes containing biocytin, whole cell recordings were obtained in hippocampal slices maintained in vitro. Hilar SOM cells containing enhanced green fluorescent protein (EGFP) were identified with fluorescent and infrared differential interference contrast video microscopy in epileptic and control GIN (E GFP-expressing Inhibitory Neurons) mice. Results showed that SOM cells from epileptic mice had 1) significant increases in somatic area and dendritic length; 2) changes in membrane properties, including a small but significant decrease in resting membrane potential, and increases in time constant and whole cell capacitance; 3) increased frequency of slowly rising spontaneous excitatory postsynaptic currents (sEPSCs) due primarily to increased mEPSC frequency, without changes in the probability of release; 4) increased evoked EPSC amplitude; and 5) increased spontaneous action potential generation in cell-attached recordings. Results suggest an increase in excitatory innervation, perhaps on distal dendrites, considering the slower rising EPSCs and increased output of hilar SOM cells in this model of epilepsy. In sum, these changes would be expected to increase the inhibitory output of surviving SOM interneurons and in part compensate for interneuronal loss in the epileptogenic hippocampus.

scholarly journals Cell type-specific isolation and transcriptomic profiling informs glial pathology in human temporal lobe epilepsy

2020 ◽  
Author(s):  
Jessica Tome-Garcia ◽  
German Nudelman ◽  
Zarmeen Mussa ◽  
Elodia Caballero ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Ex Vivo ◽  
Hybrid Population ◽  
Rna Seq ◽  
Cell Type ◽  
Fresh Frozen ◽  
Cell Type Specific

The pathophysiology of epilepsy underlies complex network dysfunction, the cell-type-specific contributions of which remain poorly defined in human disease. In this study, we developed a strategy that simultaneously isolates neuronal, astrocyte and oligodendroglial progenitor (OPC)-enriched nuclei from human fresh-frozen neocortex and applied it to characterize the distinct transcriptome of each cell type in temporal lobe epilepsy (TLE) surgical samples. Differential RNA-seq analysis revealed several dysregulated pathways in neurons, OPCs, and astrocytes, and disclosed an immature phenotype switch in TLE astrocytes. An independent single cell RNA-seq TLE dataset uncovered a hybrid population of cells aberrantly co-expressing canonical astrocyte and OPC-like progenitor markers (GFAP+OLIG2+ glia), which we corroborated in-situ in human TLE samples, and further demonstrated their emergence after chronic seizure injury in a mouse model of status epilepticus. In line with their immature signature, a subset of human TLE glia were also abnormally proliferative, both in-vivo and in-vitro. Generally, this analysis validates the utility of the proposed cell type-specific isolation strategy to study glia-specific changes ex vivo using fresh-frozen human samples, and specifically, it delineates an aberrant glial phenotype in human TLE specimens.

scholarly journals Propofol Exerts Greater Neuroprotection with Disodium Edetate than without It

2007 ◽  
Vol 28 (2) ◽  
pp. 354-366 ◽  
Author(s):  
Yoshinori Kotani ◽  
Yoshimi Nakajima ◽  
Tatsuya Hasegawa ◽  
Masahiko Satoh ◽  
Hisamitsu Nagase ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Infarct Volume ◽  
Zinc Homeostasis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Causal Mechanism ◽  
Neuroprotective Effects ◽  
Disodium Edetate

The main objective of this study, on mice, was to compare the neuroprotective effects of propofol with those of propofol plus disodium edetate (propofol EDTA). We also administered propofol EDTA (0.005% (w/v) EDTA) to mice intravenously, and measured the changes in zinc concentrations occurring after permanent middle cerebral artery occlusion. In the in vivo study, propofol EDTA displayed stronger neuroprotective effects than propofol alone. Furthermore, we examined the neuroprotective effects of EDTA administered alone, and found that EDTA Na significantly reduced the infarct volume. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells in the ischemic penumbra was reduced more by propofol EDTA than by propofol alone. We performed in the in vitro study in five groups (aerobic, vehicle (control), propofol, EDTA, and propofol plus EDTA). Propofol and EDTA each protected PC12 cells against oxygen—glucose deprivation-induced cell damage, and the effect of propofol was increased by adding EDTA. Because the chelating action of EDTA was a potential causal mechanism, we examined the effect of propofol EDTA on intracerebral zinc homeostasis. When propofol EDTA was given intravenously 10 mins before cerebral ischemia, the zinc concentration decreased significantly in the cortical area, but not in the subcortex. In conclusion, (a) propofol provides neuroprotection against both in vivo and in vitro ischemic damage, and its effects are enhanced when EDTA is added; and (b) EDTA itself protects against ischemic neuronal damage, possibly, owing to its zinc-chelating action.

scholarly journals Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R:On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298:1418–1421, 2002

2003 ◽  
Vol 14 (2) ◽  
pp. 1
Author(s):  
William T. Couldwell
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Pyramidal Cells ◽  
Rhythmic Activity ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Interictal Discharges ◽  
Human Temporal Lobe ◽  
Spontaneous Rhythmic Activity

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma-aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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