Distinct Effects of Stereotactically Injected Human Cerebrospinal Fluid Containing Glutamic Acid Decarboxylase Antibodies into the Hippocampus of Rats on the Development of Spontaneous Epileptic Activity.

Bernd Frerker,Marco Rohde,Steffen Müller,Rüdiger Köhling,Christian G Bien,Timo Kirschstein

doi:10.3390/brainsci10020123

Bernd Frerker, Marco Rohde + Show 4 more

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https://doi.org/10.3390/brainsci10020123

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Abstract

Background: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that anti-GAD autoantibodies could diminish the GABA content in the slice and facilitate epileptic activity. Methods: Cerebrospinal fluids (CSF) from two patients containing anti-GAD (A and B) were injected into the rat hippocampus in vivo. Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg2+ and/or by adding gabazine. As control groups, we injected an anti-GAD-negative human CSF or saline solution, and we used non-operated naive animals. Results: RED frequencies were significantly higher in the Mg2+-free solution than in the gabazine-containing solution. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg2+-free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. Conclusions: These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity.

Highlights

Limbic encephalitis (LE) is a syndrome composed of temporal lobe epilepsy, loss of short-term memory and psychiatric symptoms such as depression or irritability
Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg2+ and/or by adding gabazine
The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-glutamic acid decarboxylase (GAD)-B-treated and the control slices, but in the Mg2+ -free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity

Summary

Introduction

Limbic encephalitis (LE) is a syndrome composed of temporal lobe epilepsy, loss of short-term memory and psychiatric symptoms such as depression or irritability. Magnetic resonance imaging (MRI) shows unilateral or bilateral inflammation of the temporal lobe [1] This disease was described by Brierley in 1960 [2] in patients with a subacute encephalitis and usually considered to be of paraneoplastic origin [3]. The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD) Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg2+ -free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. Conclusions: These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity

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