Pathophysiology of the amygdala in epileptogenesis and epilepsy

Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Epilepsy Research (Impact Factor: 2.02). 03/2008; 78(2-3):102-16. DOI: 10.1016/j.eplepsyres.2007.11.011
Source: PubMed


Acute brain insults, such as traumatic brain injury, status epilepticus, or stroke are common etiologies for the development of epilepsy, including temporal lobe epilepsy (TLE), which is often refractory to drug therapy. The mechanisms by which a brain injury can lead to epilepsy are poorly understood. It is well recognized that excessive glutamatergic activity plays a major role in the initial pathological and pathophysiological damage. This initial damage is followed by a latent period, during which there is no seizure activity, yet a number of pathophysiological and structural alterations are taking place in key brain regions, that culminate in the expression of epilepsy. The process by which affected/injured neurons that have survived the acute insult, along with well-preserved neurons are progressively forming hyperexcitable, epileptic neuronal networks has been termed epileptogenesis. Understanding the mechanisms of epileptogenesis is crucial for the development of therapeutic interventions that will prevent the manifestation of epilepsy after a brain injury, or reduce its severity. The amygdala, a temporal lobe structure that is most well known for its central role in emotional behavior, also plays a key role in epileptogenesis and epilepsy. In this article, we review the current knowledge on the pathology of the amygdala associated with epileptogenesis and/or epilepsy in TLE patients, and in animal models of TLE. In addition, because a derangement in the balance between glutamatergic and GABAergic synaptic transmission is a salient feature of hyperexcitable, epileptic neuronal circuits, we also review the information available on the role of the glutamatergic and GABAergic systems in epileptogenesis and epilepsy in the amygdala.

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    • "According to the World Health Organization, about 50 million people may have some kind of epilepsy, being temporal lobe epilepsy (TLE) the most common form (Engel, 1998). The temporal lobe structures, such as the hippocampus, amygdala, and piriform cortex are susceptible to triggering electrical discharges contributing to brain damage and the epileptogenic mechanism (Aroniadou-Anderjaska et al., 2008). Furthermore, morphological changes such as cellular death in the CA1, mossy fiber sprouting and the dispersion of the granule cell layer have been described in both animal models and TLE patients surgical resections (Houser, 1990; Blümcke et al., 1999). "
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    ABSTRACT: Mercado-Gómez, O., et al., Role of TGF-␤ signaling pathway on Tenascin C protein upregulation in a pilocarpine seizure model. Epilepsy Res. (2014), ARTICLE IN PRESS +Model EPIRES-5232; No. of Pages 11 Epilepsy Research (2014) xxx, xxx—xxx j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / e p i l e p s y r e s Summary Seizures have been shown to upregulate the expression of numerous extracellu-lar matrix molecules. Tenascin C (TNC) is an extracellular matrix protein involved in several physiological roles and in pathological conditions. Though TNC upregulation has been described after excitotoxins injection, to date there is no research work on the signal transduction path-way(s) participating in TNC protein overproduction. The aim of this study was to evaluate the role of TGF-␤ signaling pathway on TNC upregulation. In this study, we used male rats, which were injected with saline or pilocarpine to induce status epilepticus (SE) and killed 24 h, 3 and 7 days after pilocarpine administration. For evaluating biochemical changes, we measured protein content of TNC, TGF-␤1 and phospho-Smad2/3 for localization of TNC in coronal brain hippocampus at 24 h, 3 and 7 days after pilocarpine-caused SE. We found a significant increase of TNC protein content in hippocampal homogenates after 1, 3, and 7 days of pilocarpine-caused SE, together with an enhancement of TNC immunoreactivity in several hippocampal layers and the dentate gyrus field where more dramatic changes occurred. We also observed a significant enhancement of protein content of both the TGF-␤1 and the critical downstream transduction effector phospho-Smad2/3 throughout the chronic exposure. Interestingly, animals injected with SB-431542, a TGF-␤-type I receptor inhibitor, decreased TNC content in cytosolic fraction and diminished phospho-Smad2/3 content in both cytoplasmic and nuclear fraction
    Epilepsy research 10/2014; 108(10). DOI:10.1016/j.eplepsyres.2014.09.019 · 2.02 Impact Factor
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    • "Temporal lobe epilepsy (TLE) has been associated with hippocampal sclerosis and pathological changes in the closed neighboring structures, including entorhinal cortex, amygdala and dentate gyrus [1–3]. Scalp electroencephalogram (EEG) recordings from patients with TLE usually demonstrate interictal and ictal epileptiform abnormalities over the mid/anterior temporal region [4]. "
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    ABSTRACT: Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures.
    Neural Plasticity 03/2014; 2014:675128. DOI:10.1155/2014/675128 · 3.58 Impact Factor
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    • "GABAA receptors (ligand-gated ion channels) mediate rapid inhibitory presynaptic potentials by increasing influx of chloride, and GABAB receptors (G-protein-coupled receptors) mediate slow inhibitory presynaptic potentials by increasing the potassium conductance and decreasing the calcium entry (33-35). It is hypothesized that reduction or loss of GABAergic inhibition may increase the probability of generating excitatory postsynaptic potentials and synchronizing burst discharges, and therefore induce epileptogenesis (12, 31). The GABAergic mechanisms that have been proposed include impairment of GABA release (36), changes in GABA receptors (37, 38), impairment of GABA synthesis (39, 40) and neuronal loss (41, 42). "
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    ABSTRACT: Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models.
    Iranian Journal of Basic Medical Science 11/2013; 16(11):1119-1132. · 1.23 Impact Factor
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