title: Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.
abstract: OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel-treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel-treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel-treated group. There was a decreased presence of inflammatory cells in the HA hydrogel-treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Sergiy V
authors.initials: SV
authors.lastname: Kushchayev
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Morgan B
authors.initials: MB
authors.lastname: Giers
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona; and.
authors.forename: Doris
authors.initials: D
authors.lastname: Hom Eng
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Nikolay L
authors.initials: NL
authors.lastname: Martirosyan
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Eschbacher
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Martin M
authors.initials: MM
authors.lastname: Mortazavi
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Theodore
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix;
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015331:Cohort Studies; D004195:Disease Models, Animal; D006820:Hyaluronic Acid; D020100:Hydrogels; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: BBB = Basso, Beattie, and Bresnahan; DTP = 3,3′-dithiobis (propanoic acid); DTT = dithiothreitol; HA = hyaluronic acid; PBS = phosphate-buffered saline; PEGDA = poly(ethylene glycol)-diacrylate; R/L = right/left; SCI = spinal cord injury; SEM = scanning electron microscope; TEM = transmission electron microscopy; hyaluronic acid; lesion size; neuroprotective; rat; red nucleus; retrograde tracing; spinal cord injury