chondroitin-sulfates and Intracranial-Arteriosclerosis

The aim of this study was to propose a classification system for childhood arterial ischaemic stroke (AIS). Subtypes from the Trial of Org 10172 in Acute Stroke Therapy (TOAST) classification, previously shown to be applicable to children, were retained in the proposed Paediatric Stroke Classification (PSC). Additional important paediatric AIS aetiologies were identified from a literature review. Preliminary validation was performed by three raters who categorized clinical vignettes from 135 patients (66 male; median age 6.3 y, range 0.1 to 16 y). Eight aetiological subtypes were identified and defined, as follows: (1) sickle cell disease; (2) cardioembolic; (3) moyamoya syndrome; (4) cervical arterial dissection; (5) steno-occlusive cerebral arteriopathy; (6) other determined aetiology; (7) multiple probable/possible aetiologies; and (8) undetermined aetiology. There was very good agreement between the raters about categorization of the vignettes. Causes of disagreement were identified and final categories and definitions were modified accordingly. We conclude that the PSC enables the categorization of children with AIS into aetiological subtypes relevant to this age group. This will be useful in multicentre studies of natural history and treatment but will require further independent validation.

Topics: Adolescent; Anemia, Sickle Cell; Brain Ischemia; Carotid Artery, Internal, Dissection; Cerebral Infarction; Child; Child, Preschool; Chondroitin Sulfates; Data Collection; Dermatan Sulfate; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Infant; Infant, Newborn; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Moyamoya Disease; Reproducibility of Results; Review Literature as Topic; Severity of Illness Index; Stroke

The glycosaminoglycan (GAG) content of normal and atherosclerotic areas of cerebral arterial tissue isolated from human males was measured. The main trunk and distal branches of the arteries were obtained at autopsy on 12-89-year-old Japanese subjects. The GAG components were analysed by high-performance liquid chromatography (HPLC) after enzymatic digestion, using specific GAG lyases. Both total GAGs and water content were lower in the diseased arteries than those in the normal state. In contrast, the reverse was noted for the lipid content. The main GAG component of the normal cerebral arteries was heparan sulfates (HS), comprising half the total GAGs, followed by dermatan sulfate (DS) and chondroitin 6-sulfate (Ch-6S) constituting 1/5 to 1/9 the total GAGs. Chondroitin 4-sulfate (Ch-4S) comprised approx. 1/10 the total GAGs. Oversulfated chondroitin sulfate isomers were detected as novel peaks of the chondroitin sulfate types G, B, E and H on HPLC analysis. Small amounts of hyaluronic acid (HA) and chondroitin were also detected. The total GAG content decreased with severity of atherosclerosis. The content and proportions of HS to the total GAGs decreased remarkably, and those of Ch-4S, HA and chondroitin showed a moderate decrease. The reverse was the case for those of DS, Ch-6S and oversulfated DS and/or Ch-S. The lipid components, in particular cholesterol ester, in the diseased tissue were significantly greater than in the visibly normal parts while the opposite was the case for the water content. Thus, the GAG species and their contents in human cerebral arteries showed a characteristic distribution. As oversulfated DS and Ch-S isomers have anticoagulant and anti-atherosclerotic activities, they may play a pertinent role in the disease process.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Body Water; Cerebral Arteries; Child; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Glycosaminoglycans; Humans; Intracranial Arteriosclerosis; Japan; Lipids; Male; Middle Aged

The binding to plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of chondroitin sulfate (CS) and heparin sulfate (HS), isolated from cerebral arteries and aortas, was studied. The binding of CS to LDL was higher than that of HS and neither bound to HDL. CS from cerebral arteries contained a higher percentage of iduronic residues (IDUA-Ga1NAc 4S) and a lower percentage of G1cUA-Ga1NAc 4S, and bound more strongly to LDL than CS from aortas. Our results suggest a strong dermatan sulfate (DS) activity on binding to LDL.

Topics: Aorta; Cerebral Arteries; Chondroitin Sulfates; Chromatography, Gel; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Heparin; Humans; In Vitro Techniques; Intracranial Arteriosclerosis; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Male; Molecular Weight