Cytotoxicity of ventricular cerebrospinal fluid from Parkinson patients: correlation with clinical profiles and neurochemistry.
Other investigators have reported that the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) might contain endogenous dystrophic factors. Using CSF samples drawn from individual PD patients during surgery, we investigated the toxic effect of ventricular CSF (vCSF) on the growth of PC12 cells and the correlation between the clinical profiles of the patients and CSF neurochemistry. Ventricular CSF samples from 28 patients with PD or essential tremor (ET) were collected during ventriculography for stereotactic pallidotomy or thalamotomy. PC12 cells were incubated with 20% vCSF from both clinical groups for up to 72 h. Microdialysis was used to analyze four neurochemical parameters (glucose, lactate, pyruvate, and glutamate) in each vCSF sample. We observed that vCSF drawn from PD patients exerted nonspecific growth inhibition on PC12 cells in a time-dependent manner. The growth inhibitory action of PD-vCSF decreased significantly after heat treatment. Microdialysis demonstrated no statistical differences between PD and ET samples among the four parameters studied. In addition, PC12 cell survival after 72 h incubation with PD-vCSF correlated with no neurochemical parameter or individual clinical profile (age, onset age, duration of disease, Hoehn & Yahr stage, disease progression rate), except for a slight correlation between vCSF and disease progression rate in heat treated samples from female patients. One or more endogenous cytotoxic factors in PD-vCSF inhibit PC12 cell growth. This factor or factors are partially sensitive to heat which suggests proteins or peptides as possible agents. The cytotoxic effect of PD-vCSF did not directly correlate with any clinical profiles studied or energy metabolism of PD brain.
Mandybur
George T
GT
Department of Neurosurgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216-4505, USA. gmandybur@neurosurgery.umsmed.edu
Miyagi
Yasushi
Y
Yin
Wei
W
Perkins
Eddie
E
Zhang
John H
JH
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002556:Cerebrospinal Fluid Proteins / Q000737:chemistry*; D018450:Disease Progression; D020329:Essential Tremor / Q000134:cerebrospinal fluid*; D005260:Female; D005947:Glucose / Q000032:analysis; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D016716:PC12 Cells; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D051381:Rats
D000596:Amino Acids; D002556:Cerebrospinal Fluid Proteins; D005947:Glucose