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

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 Mg 2+ 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 Mg 2+ -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 Mg 2+ -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.

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

“…Carbogen (95% O 2 , 5% CO 2 ) gassed solution serves this purpose. Good cell survival has been shown in brain tissue [48][49][50], in the Langendorff perfusion system [33,34,51], and in the organ bath [52], especially when using intestinal tissue [53] or esophageal sections [54][55][56]. One study [57] reported toxic effects of 95% O 2 in prolonged esophageal cell cultures, but these results have not been replicated [58].…”

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters

“…Tyrosine hydroxylase (TH) and glutamate decarboxylase 67 (GAD67) are the rate-limiting enzymes for the production of excitatory and inhibitory neurotransmitters in the central nervous system [ 29 , 30 ]. The production of excitatory neurotransmitters, such as dopamine and NE in the brain, depends on TH [ 31 ].…”

“…The production of excitatory neurotransmitters, such as dopamine and NE in the brain, depends on TH [ 31 ]. GAD67 promotes the degradation of glutamate (Glu) and accelerates the production of inhibitory neurotransmitter γ-aminobutyric acid (GABA) [ 30 ]. Our laboratory studies and those of others have shown increased TH expression and decreased GAD67 expression in the PVN during hypertension [ 32 ] and heart failure [ 33 ], causing an imbalance between excitatory and inhibitory neurotransmitters [ 34 ].…”