Iron-induced experimental cortical seizures: Electroencephalographic mapping of seizure spread in the subcortical brain areas

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 synchronously propagated into the studied subcortical brain areas. Seizure behaviours seemed to increase in correspondence with the spread of the epileptic electrographic activity in subcortical areas. Comparison of the cortical focus electroencephalographic and associated multiple-unit action potential recordings with those from the subcortical structures showed that the occurrence and evolution of the epileptiform activity in the subcortical structures were in parallel with that in the cortical focus. The intracerebral anatomic progression and delineation of seizure spread (mapped by field potential (EEG) and multiple-unit action potentials (MUA) recordings) indicated participation of these regions in the generalization of seizure activity in this model of epilepsy. The seizure-induced activation of the hippocampus appeared to evolve into an epileptic focus independent of the cortical focus. The present study demonstrates the propagation of epileptic activity from the cortical focus into the limbic and basal ganglia regions. Treatment of iron-induced epileptic rats with ethosuximide, an anti-absence drug, resulted in suppression of the epileptiform activity in the cortical focus as well as in the subcortical brain areas.

Comparison of the antiepileptogenic effects of an early long‐term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy

“…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).…”

Epilepsy and Epileptic Syndrome

“…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.…”

Nanoscale intracortical iron injection induces chronic epilepsy in rodent

“…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, ).…”