title: Hyaluronan tetrasaccharide in the cerebrospinal fluid is associated with self-repair of rats after chronic spinal cord compression.
abstract: The objective of this study was to explore changes in hyaluronan levels in the cerebrospinal fluid (CSF) in a spinal cord compression model, to investigate whether hyaluronan tetrasaccharide was involved in this process, and to test the effects of hyaluronan tetrasaccharide on neuron and oligodendrocyte repair. We developed a chronic spinal cord compression model with various sizes of polymer sheets (1.5×0.7×0.3 mm(3); 5×1.5×0.7 mm(3)) that were implanted microsurgically underneath the C(5-6) laminae. The rats were divided into three groups: a sham group, a mildly compressed (MC) group, and a widely compressed (WC) group. Locomotor functional evaluations revealed that the behavioral function of the MC and WC groups dropped to their lowest level from the fourth to fifth week and gradually recovered thereafter. The hyaluronan levels in the CSF gradually increased after spinal cord compression. Furthermore, hyaluronan tetrasaccharide was involved in the hyaluronan change. In addition, we found that nuclear factor kappa B (NF-κB) and cellular inhibitor-of-apoptosis protein 2 (c-IAP(2)) were co-expressed in neurons and oligodendrocytes, and caspase-3 expression gradually decreased in the compression model. The brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) expression was upregulated in astrocytes at the fourth week post-compression. Hyaluronan tetrasaccharide (HA(4)) induced NF-κB and c-IAP(2) to suppress the H(2)O(2)-induced apoptosis in primary neuronal cultures and increased BDNF and VEGF expression in astrocytic cultures in vitro. These findings suggest that HA(4) in the CSF may associate with behavioral recovery by increasing the levels of NF-κB, c-IAP(2), and neurotrophic factors after chronic spinal cord compression.
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Rong
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: G
authors.initials: G
authors.lastname: Dang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Wei
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002908:Chronic Disease; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D006820:Hyaluronic Acid / Q000134:cerebrospinal fluid*; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013117:Spinal Cord Compression / Q000134:cerebrospinal fluid*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D009414:Nerve Growth Factors; D006820:Hyaluronic Acid