Developmental and Age‐Related Changes in Rat Brain Glycosaminoglycans

Abstract

The quantities of each major class of glycosaminoglycan were determined in rat cerebrum from postnatal day 5 to 30 months of age. Chondroitin sulphate, dermatan sulphate, heparan sulphate, heparin, and hyaluronate were found, but no keratan sulphate was detected. Large and rapid changes in glycosaminoglycan content were observed during the period of brain maturation, and thereafter relatively steady levels were maintained until after the age of 12 months. The most remarkable change in the aged rat cerebrum was the ratio by weight of hyaluronate to chondroitin sulphate, which was approximately 1:1 from postnatal day 10 to 18 months but increased to 2.6:1 by the age of 30 months. In immature rats, the proportion of nonsulphated and 6-sulphated disaccharides derived from chondroitinase AC digests of brain glycosaminoglycans was much greater than in adults. In mature rats, chondroitin sulphate was composed almost entirely of 4-sulphated disaccharide subunits. The possibility that these changes could affect the permeability properties of the cerebral extracellular space and ionic equilibria in the brain is discussed.

Fixed negative charge and the Donnan effect: a description of the driving forces associated with brain tissue swelling and oedema

“…This assay has been used with success to measure FCD values for comparison with FCD predictions in tissues modelled as triphasic mixture materials, such as cartilage and aorta (Lu et al 2007;Azeloglu et al 2008). While GAGs may not represent the entirety of the FCD found within brain (other contributions may come from negatively charged DNA, proteins and matrix molecules), there is a significant amount of different sulphated proteglycans in brain, the majority of which contain chondroitin sulphate (Margolis et al 1975(Margolis et al , 1976Jenkins & Bachelard 1988;Lander 1993;Koppe et al 1997;Costa et al 2007). Much of this sulphated GAG, especially at later stages of development, has been localized within the cytoplasm of neurons and astrocytes (Margolis et al 1979;Alvarado & Castejon 1984;Aquino et al 1984;Sames & Hoyer 1992).…”

Brain Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

“…HA proved to be the dominant GAG in the preterm brain, accounting for more than 60% of the GAGs, but its relative amount decreased gradually after birth at term gestation to reach the adult level of about 40% [32,34]. GAGs, especially HA, have been implicated in the morphogenesis and maturation of the brain by providing highly hydrated matrices for cellular growth, proliferation, and migration [31,33] as well as for cell-to-cell interaction [35].…”

“…Content and composition of brain GAGs undergo developmental changes [29][30][31][32][33][34]. Total GAGs are constant at early stages of development and thereafter increase steadily to attain a plateau by the postneonatal period.…”

In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate

“…Normal brain ECM is composed mostly of hyaluronic acid, a nonsulfated glycosaminoglycan, and proteoglycans carrying either chondroitin sulfate (CSPG) or heparan sulfate (HSPG) glycosaminoglycan side chains, along with the more recently identified reelin and tenascin glycoproteins (4,5). Although aging (6)(7)(8), pathological insults (9, 10), or genetic modifications (11) resulting in altered brain ECM content are often associated with changes in ECS volume fraction, the ability of ECM components to specifically bind and slow the migration of diffusing substances in the ECS remains an open question. A direct ECM effect on extracellular diffusion (e.g., sequestration or slowing of a diffusing substance) has been postulated for proteins capable of binding HSPG (12,13), but little evidence exists for this phenomenon in vivo.…”