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Cerebrospinal fluid from multiple sclerosis patients inactivates neuronal Na+ current
H Köller1, J Buchholz, M Siebler
1Heinrich-Heine University, Department of Neurology, Düsseldorf, Germany.
Brain : a Journal of Neurology
|April 1, 1996
Summary
Cerebrospinal fluid from multiple sclerosis patients alters neuronal sodium currents, reducing excitability. These findings suggest a mechanism for transient neurological symptoms in active multiple sclerosis.
Area of Science:
- Neuroscience
- Immunology
- Neurology
Background:
- Multiple sclerosis (MS) is a common central nervous system (CNS) inflammatory disease.
- Immunologically active molecules in cerebrospinal fluid (CSF) of MS patients are known, but their role in neuronal dysfunction, particularly transient symptoms, remains unclear.
Purpose of the Study:
- To investigate the effect of CSF from MS patients on neuronal membrane currents.
- To compare these effects with CSF from patients with non-inflammatory neurological diseases.
Main Methods:
- Cultured cortical neurons from embryonic rats were exposed to CSF from 13 MS patients and 12 non-inflammatory neurological disease patients.
- Membrane currents, specifically Na+ current (INa) inactivation, were measured.
- Effects were assessed for reversibility and heat sensitivity.
Main Results:
- CSF from MS patients significantly increased Na+ current (INa) inactivation, shifting the inactivation curve to more hyperpolarizing potentials (mean shift of 9.3 mV, range 4.3–17.6 mV).
- This effect was reversible upon washing and abolished by heat inactivation of the CSF.
- The magnitude of the shift correlated with the IgG index but not with pleocytosis, protein, or albumin levels.
Conclusions:
- Diffusible factors in the CSF of MS patients reduce neuronal excitability.
- These factors likely contribute to the transient neurological symptoms observed in active MS.
- The findings highlight a potential mechanism for neuronal network disturbance in MS.