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; Christian G Bien; Rüdiger Köhling; Timo Kirschstein

doi:10.3390/brainsci10020123

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

Brain Sci. 2020 Feb 22;10(2):123. doi: 10.3390/brainsci10020123.

Authors

Bernd Frerker^{1

2}, Marco Rohde¹, Steffen Müller¹, Christian G Bien³, Rüdiger Köhling^{1

4}, Timo Kirschstein^{1

4}

Affiliations

¹ Oscar Langendorff Institute of Physiology, University of Rostock, 18057 Rostock, Germany.
² Department of Irradiation Therapy, University Hospital of Rostock, 18059 Rostock, Germany.
³ Epilepsy Center Bethel, Krankenhaus Mara, 33617 Bielefeld, Germany.
⁴ Center of Transdisciplinary Neurosciences Rostock, University of Rostock, 18147 Rostock, Germany.

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.

Keywords: NMDA and GABA receptor; autoimmune limbic encephalitis; field potential recording; glutamic acid decarboxylase; hippocampus of rats; human cerebrospinal fluid; recurrent epileptiform discharges.