Abstract:The iron-induced model of post-traumatic chronic focal epilepsy in rats was studied by depth-electrode mapping to investigate the spread of epileptiform activity into subcortical brain structures after its onset in the cortical epileptic focus. Electrical seizure activity was recorded in the hippocampal CA1 and CA3 areas, amygdala and caudate-putamen, in rats with iron-induced chronic cortical focal epilepsy. These experiments showed that the epileptiform activity with its onset in the cortical focus synchrono… Show more
“…We suggest that both drugs could, in different ways, be acting on a proposed hyperexcited area of cortical epileptic focus and block or reduce adaptive alterations leading to development of generalized absence epilepsy. In keeping with this, treatment of focal ironinduced epileptic rats with ETH has been shown to suppress epileptiform activity in the cortical focus as well as in subcortical brain areas (Sharma et al, 2007). A similar direct effect of LEV has yet to be demonstrated, although it is known to be particularly effective in refractive partial epilepsy patients (Gambardella et al, 2008).…”
SUMMARYPurpose: Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long-term treatment with some established antiabsence drugs might prevent the development of seizures, and whether such an effect could be sustained.Methods: WAG/Rij rats were treated for 3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad-spectrum AED with antiabsence and antiepileptogenic properties). Results: We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model. Discussion: These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.
“…We suggest that both drugs could, in different ways, be acting on a proposed hyperexcited area of cortical epileptic focus and block or reduce adaptive alterations leading to development of generalized absence epilepsy. In keeping with this, treatment of focal ironinduced epileptic rats with ETH has been shown to suppress epileptiform activity in the cortical focus as well as in subcortical brain areas (Sharma et al, 2007). A similar direct effect of LEV has yet to be demonstrated, although it is known to be particularly effective in refractive partial epilepsy patients (Gambardella et al, 2008).…”
SUMMARYPurpose: Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long-term treatment with some established antiabsence drugs might prevent the development of seizures, and whether such an effect could be sustained.Methods: WAG/Rij rats were treated for 3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad-spectrum AED with antiabsence and antiepileptogenic properties). Results: We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model. Discussion: These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.
“…92 Indeed, intracortical injection of iron (ferric chlorides) in the rat brain has been used as a post-traumatic epilepsy model. 93,94 Other animal models ofpost-traumatic epilepsy include the lateral fluid percussion and the controlled cortical impact models. These demonstrate neurodegeneration, neurogenesis, astrocytosis, microgliosis, axonal, myelin injury, axonal sprouting, vascular damage and angiogenesis in the injured cortex, perifocal area, underlying hippocampus and/or thalamus.…”
Section: Neurodegenerative Changes In Epilepsies: Cellular and Molecumentioning
Epilepsy is one of the most common neurological disorders. In most patients with epilepsy, seizures respond to available medications. However, a significant number of patients, especially in the setting of medically-intractable epilepsies, may experience different degrees of memory or cognitive impairment, behavioral abnormalities or psychiatric symptoms, which may limit their daily functioning. As a result, in many patients, epilepsy may resemble a neurodegenerative disease. Epileptic seizures and their potential impact on brain development, the progressive nature of epileptogenesis that may functionally alter brain regions involved in cognitive processing, neurodegenerative processes that relate to the underlying etiology, comorbid conditions or epigenetic factors, such as stress, medications, social factors, may all contribute to the progressive nature of epilepsy. Clinical and experimental studies have addressed the pathogenetic mechanisms underlying epileptogenesis and neurodegeneration.We will primarily focus on the findings derived from studies on one of the most common causes of focal onset epilepsy, the temporal lobe epilepsy, which indicate that both processes are progressive and utilize common or interacting pathways. In this chapter we will discuss some of these studies, the potential candidate targets for neuroprotective therapies as well as the attempts to identify early biomarkers of progression and epileptogenesis, so as to implement therapies with early-onset disease-modifying effects.
“…Injected iron causes oxidative stress in neural tissue, leading to membrane lipid peroxidation and a decrease in astrocytic uptake of glutamic acid. As a result, the level of glutamate receptor‐mediated excitation increases, resulting in posttraumatic epileptogenesis (Triggs and Willmore, ; Sharma et al, ; Jyoti et al, ). Recurrent epileptiform activity, along with behavioral convulsions, is common in iron‐induced epileptic animals (Willmore et al, ; Sharma et al, ).…”
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