title: The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis.
abstract: Traumatic spinal cord injury (SCI) comprises a heterogeneous condition caused by a complex array of mechanical forces that damage the spinal cord - making each case somewhat unique. In addition to parenchymal injury, a subset of patients experience severe inflammation in the subarachnoid space or arachnoiditis, which can lead to the development of fluid-filled cavities/syringes, a condition called post-traumatic syringomyelia (PTS). Currently, there are no therapeutic means to address this devastating complication in patients and furthermore once PTS is diagnosed, treatment is often prone to failure. We hypothesized that reducing subarachnoid inflammation using a novel bioengineered strategy would improve outcome in a rodent model of PTS. A hydrogel of hyaluronan and methyl cellulose (HAMC) was injected into the subarachnoid space 24 h post PTS injury in rats. Intrathecal injection of HAMC reduced the extent of fibrosis and inflammation in the subarachnoid space. Furthermore, HAMC promoted improved neurobehavioural recovery, enhanced axonal conduction and reduced the extent of the lesion as assessed by MRI and histomorphometric assessment. These findings were additionally associated with a reduction in the post-traumatic parenchymal fibrous scar formation as evidenced by reduced CSPG deposition and reduced IL-1α cytokine levels. Our data suggest that HAMC is capable of modulating inflammation and scarring events, leading to improved functional recovery following severe SCI associated with arachnoiditis.
authors.affiliation: Institute of Medical Science, University of Toronto, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Austin
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Kang
authors.forename: M Douglas
authors.initials: MD
authors.lastname: Baumann
authors.forename: Lisa
authors.initials: L
authors.lastname: DiDiodato
authors.forename: Kajana
authors.initials: K
authors.lastname: Satkunendrarajah
authors.forename: Jefferson R
authors.initials: JR
authors.lastname: Wilson
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stanisz
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000818:Animals; D001100:Arachnoiditis / Q000188:drug therapy* / Q000276:immunology; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid