Epileptiform activity induced by low extracellular magnesium in the human cortex maintained in vitro

Abstract

Extracellular field potentials and [K+]o were recorded in slices of human epileptogenic neocortex maintained in vitro during perfusion with Mg(2+)-free artificial cerebrospinal fluid (ACSF). The human neocortex was obtained during neurosurgical procedures for the relief of seizures that were resistant to medical treatment. Spontaneous epileptiform activity and episodes of spreading depression appeared within 1.5 to 2 hours of perfusion with Mg(2+)-free ACSF. The epileptiform discharges consisted of negative field potential shifts (amplitude, 0.8-10 mV) that lasted 2.5 to 80 seconds and recurred at intervals ranging between 4 and 160 seconds. Both duration and frequency of occurrence of epileptiform events were not significantly different when measured in slices obtained from spiking tissue compared with those gathered from nonspiking neocortical areas. Transient increases in [K+]o of up to 10.5 mM were associated with each epileptiform discharge; these changes were maximal and fastest in the middle neocortical layers. Spreading depression episodes were characterized by 20 to 30-mV negative shifts that lasted up to 200 seconds and were accompanied by increases in [K+]o of approximately 100 mM. Epileptiform discharges and spreading depressions did not occur during perfusion with Mg(2+)-free ACSF that contained either competitive or noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor subtype. In contrast, pharmacological blockade of non-NMDA receptors did not influence the epileptiform activity observed in Mg(2+)-free ACSF. These findings demonstrate that decreasing [Mg2+]o leads to the appearance of both spontaneous epileptiform discharges and spreading depression in the human epileptogenic neocortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronically Epileptic Human and Rat Neocortex Display a Similar Resistance Against Spreading Depolarization In Vitro

“…18 Consistently, SD co-occurs typically in models for acute status epilepticus. 20,21 Similar observations also exist in patients with acute neuronal injury in whom SDs were significantly more abundant than epileptic activities, but SDs always co-occurred with epileptic ictaform activity whenever epileptic ictaform activity was detected. 22 In contrast, resistance against SD seems to increase in models for chronic epilepsy such as the pentylenetetrazole model or that of prolonged blood brain-barrier disruption in rats.…”

Spreading Depolarization, A Pathophysiological Mechanism of Stroke and Migraine Aura

“…In the field of migraine, this era continued in the early 1980s with the first recordings of the normal neurovascular response to spreading depolarization in patients undergoing migraine aura by Olesen and colleagues [79]. In the early 1990s, Avoli and colleagues provided the first evidence of spreading depolarizations in human brain slices from patients with intractable epilepsy [80], later confirmed by a number of other studies [81,82]. Moreover, the first gene responsible for familial hemiplegic migraine was identified [83][84][85].…”

“…Only much later, it became obvious that this was an incorrect assumption. There are in fact several common pathways for the induction of epileptic burst discharges and spreading depolarization in experimental models for acute hyperexcitability, such as decrease in extra cellular magnesium or inhibition of GABA receptors [80,102]. However, chronic epilepsy is very different from acute hyperexcitability.…”

Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

“…Neocortical brain slices treated with bicuculline (BCC) or magnesium-free solutions serve as acute models of neocortical epilepsy in vitro, because they produce both interictal-like depolarizing paroxysmal shift (PDS) discharges and seizurelike events (Avoli et al 1991;Hablitz 1987;Schiller 2002Valenzuela and Benardo 1995). In this study, we used extracellular field potential measurements and whole cell intracellular voltage recordings from neocortical brain slices treated with either BCC or magnesium-free solution to investigate the antiepileptic effects of two stimulation paradigms: sustained low-frequency stimulation (0.1-5 Hz for 5 min or longer), which is best suited for prolonged open-loop stimulation, and short trains of high-frequency stimulation (25-200 Hz for 1-5 s), which is best suited for closed-loop stimulation.…”