Introduction: We designed a thermo-sensitive, biodegradable chitosan-gelatin hydrogel for neuroprotection and growth factor delivery after neurotrauma. The functional outcomes were evaluated after application of this hydrogel in rat model of severe spinal cord injury
Methods: Adult SD rats were randomly assigned to a control (spinal cord injury only) and two experimental groups (topical hydrogel, and topical hydrogel with GDNF). We induced severe contusion spinal cord injury by a computer-controlled impactor. In the topical group, hydrogel solution was placed on the cord surface at the lesion epicenter. All animals were followed for 12 weeks and weekly behavioral testing was performed using the BBB scale (minimum 0, maximum 21). Immunohistochemistry was performed to study scar formation, and tissue preservation.
Results: The application of hydrogel did not adversely affect the functional outcomes. The BBB scores were significantly better in the topical group as compared to the control group. Inclusion of GDNF further improved functional outcomes. Immunohistochemistry revealed preservation of neuronal bridge across the injury epicenter.
Conclusions: The application of chitosan-gelatin hydrogel improves functional outcomes when combined with GDNF in a rat model of severe spinal cord injury. Further studies are warranted to optimize its effects and evaluate in large animal models.
Patient Care: The chitosan-gelatin hydrogel has a potential for clinical application for neuroprotection after spinal cord injury.
Learning Objectives: Topical application of chitosan-gelatin hydrogel improves functional outcomes after severe contusion spinal cord injury in rats.
References: 1. National Spinal Cord Injury Statistical Center (NSCISC). Spinal Cord Injury Facts and Figures at a Glance. Birmingham: University of Alabama; 2010 [updated February 2010; cited 2010 August 23]; Available from: https://www.nscisc.uab.edu/.
2. Fehlings MG, Baptiste DC. Current status of clinical trials for acute spinal cord injury. Injury. 2005;36 Suppl 2:B113-22.
3. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: a reappraisal. Neurorx. 2004;1(1):80-100.
4. Onose G, Anghelescu A, Muresanu DF, et al. A review of published reports on neuroprotection in spinal cord injury. Spinal Cord. 2009;47(10):716-26.
5. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991;75(1):15-26.
6. Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA. 1984;251(1):45-52.
7. Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med. 1990;322(20):1405-11.
8. Nomura H, Tator CH, Shoichet MS. Bioengineered strategies for spinal cord repair. J Neurotrauma. 2006;23(3-4):496-507.
9. Yoshii S, Oka M, Shima M, Taniguchi A, Taki Y, Akagi M. Restoration of function after spinal cord transection using a collagen bridge. J Biomed Mater Res A. 2004;70(4):569-75.
10. Itosaka H, Kuroda S, Shichinohe H, et al. Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord: a novel material for CNS tissue engineering. Neuropathology. 2009;29(3):248-57.
11. Pan HC, Cheng FC, Lai SZ, Yang DY, Wang YC, Lee MS. Enhanced regeneration in spinal cord injury by concomitant treatment with granulocyte colony-stimulating factor and neuronal stem cells. J Clin Neurosci. 2008;15(6):656-64.
12. Piantino J, Burdick JA, Goldberg D, Langer R, Benowitz LI. An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp Neurol. 2006;201(2):359-67.
13. Cho Y, Shi R, Borgens RB. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury. J Exp Biol. 2010;213(Pt 9):1513-20.
14. Horn EM, Theodore N, Assina R, Spetzler RF, Sonntag VK, Preul MC. The effects of intrathecal hypotension on tissue perfusion and pathophysiological outcome after acute spinal cord injury. Neurosurg Focus. 2008;25(5):E12.
15. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1-21.
16. Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol. 1996;139(2):244-56.