Induction of apoptosis by cerebrospinal fluid from patients with primary-progressive multiple sclerosis in cultured neurons.
We have studied the noxious effect of cerebrospinal fluids (CSF) from patients with primary-progressive multiple sclerosis (MS) on cultured neurons. Cells were exposed to CSF for 8 days and the possible neuronal damage was determined. Morphological studies with phase-contrast microscopy showed cellular shrinkage indicating apoptosis. CSF-induced apoptosis as evidenced by the fluorescent DNA-binding dye Hoechst 33342, as well as by the TUNEL-reaction, was only present in primary-progressive MS patients with a worsening disease. This neuron injury did not correlate with blood-brain barrier dysfunction nor with intrathecal IgG synthesis. On the contrary, CSF from either stable primary-progressive or other non-inflammatory neurological diseases, did not induce any culture damage. Undetectable or low similar tumor necrosis factor-alpha (TNF-alpha) levels (range to 8.7 pg/ml) were found in the CSFs tested regardless they damage cultures or not. These results suggest that soluble factors, other than TNF-alpha, molecules transudated from blood or IgG, present in the CSF of active primary-progressive patients with MS induce neuronal apoptosis.
Alcázar
A
A
Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
Regidor
I
I
Masjuan
J
J
Salinas
M
M
Alvarez-Cermeño
J C
JC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001562:Benzimidazoles; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000502:physiology; D018450:Disease Progression; D005456:Fluorescent Dyes; D020287:In Situ Nick-End Labeling; D008858:Microscopy, Phase-Contrast; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000145:classification / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid; D009474:Neurons / Q000502:physiology*; D051381:Rats / Q000196:embryology
D001562:Benzimidazoles; D005456:Fluorescent Dyes; C017807:bisbenzimide ethoxide trihydrochloride