Gangliosides of human cerebrospinal fluid in various neurologic diseases

Abstract

Simultaneous profile determination and quantification of human cerebrospinal fluid (CSF) gangliosides in various neurologic diseases ( n = 71) was examined. Gangliosides were extracted with methanol/chloroform from clinically available amounts of CSF (4–5 ml), then separated and quantified by high-performance thin-layer chromatography (HPTLC) and direct densitometry. Based on chromatographic comparison with standards, the percentage of lipid-bound NeuAc positive fractions in ‘normal’ CSF samples were: GM1 (II 3 NeuAc-GgOse 4Cer) (3%); GD3 (II 3 NeuAc 2-Lac-Cer) (4%); GD1a (IV 3 NeuAc, II 3 NeuAc-GgOse 4 Cer) (15%); X1 (3%); GD1b (II 3(NeuAc) 2-GgOse 4 Cer) (16%); X2 (4%); GT1b (IV 3 NeuAc, II 3(NeuAc) 2-GgOse 4-Cer) (40%); and GQ1b (IV 3(NeuAc) 2, II 3(NeuAc) 2 – GgOse 4-Cer (15%). Similarity between CSF and human cerebellar cortex, particularly in proportion of “b” series gangliosides (GQ1b, GT1b, GD1b), could be observed. A higher proportion of GD1a ganglioside, with decreased GQ1b was found in infancy. The total ganglioside content (mean ± 2 SD) varied between 645–894 μg/1. Significant alterations of the CSF ganglioside profile, with an increase in less polar gangliosides, GM3 and GD3, correlated with the blood-brain barrier dysfunction (CSF hemorrhages, compressive syndrome), or some malignant processes (metastatic brain melanoma). A statistically significant increase in the content of total CSF gangliosides was found in the following groups of patients as compared to controls: (1) ischemic cerebrovascular accident (CVI) with good outcome ( P < 0.02); (2) peripheral neuropathy and polyneuropathy ( P < 0.001) and (3) intravertebral discopathy ( P < 0.05). A significant decrease in the content of total CSF gangliosides was found in CVI group with lethal outcome ( P < 0.05).