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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Available from: Brita Fritsch
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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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    • "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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    • "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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