Dr. Hanna’s lab investigates novel interventions to improve functional recovery after spinal cord injury (SCI). After SCI, there is immediate mechanical damage followed by a secondary damage causing tissue degeneration and a dense scar. This dense scar is one of the primary reasons that axons fail to regenerate after SCI. One area of our research involves the use of peripheral nerve grafts to serve as scaffolds for axonal growth in order to bridge the glial scar. Peripheral nerve grafts provide several advantages when used as scaffolds; they contain Schwann cells that can myelinate regenerating axons as well as several growth factors that have been shown to promote axonal growth. A second area of our research for SCI treatment involves the use of mineral coatings on microparticles to achieve a sustained release of therapeutic proteins directly in the injury site. The specific therapeutic proteins that we are currently researching include:
- Interleukin-10, an anti-inflammatory cytokine that has been shown to attenuate secondary damage by reducing the synthesis of pro-inflammatory cytokines.
- Chondroitinase ABC, a bacterial enzyme used to digest chondroitin sulfate glycosaminoglycans, which are one of the main inhibitory molecules in the glial scar.
- Neurotrophin-3, a growth factor that has been shown to induce axonal sprouting and promote axonal growth.
Although autologous nerve grafts are the gold standard for treating large peripheral nerve gaps created during trauma, generally patients only regain a small portion of function in limbs affected by the injury. The overall goal of our research is to promote more axonal growth and increase the rate of axon growth through an autologous graft via sustained delivery of biologically active growth factors at the distal end of the graft. A unique aspect of our approach is the use of mineral coated microparticles to deliver the growth factors. These mineral coatings are highly adaptable and the growth factor release kinetics can be tailored for the time needed to grow the axons the length of the graft. The specific growth factors that we are currently researching include:
- Glial derived neurotrophic factor, a growth factor that has been shown to induce axon growth from motor neurons.
- Nerve growth factor, a growth factor that has been shown to induce axon growth from dorsal root ganglion neurons.
Peripheral Nerve Grafts and Chondroitinase ABC Application Improves Functional Recovery After Complete Spinal Cord Transection
Hanna, A., Kaeppler, K.E., Ehlers, M.E., Dadsetan, M.D., Yaszemski, M.J., Toigo, T.D., Kim, J., Hwang, E., Bogarin-Miranda, E., Buchholz, M.M., Springer, A.R., and Hellenbrand, D.J.
Journal of Neurology Research, 2013, 3(3-4):85-95
The Therapeutic Role of Interleukin-10 after Spinal Cord Injury
Thompson CD, Zurko JC, Hanna BF, Hellenbrand DJ, and Hanna A.
Journal of Neurotrauma. 2013, 30(15):1311-24.
Basic Techniques for Long Distance Axon Tracing in the Spinal Cord
Hellenbrand, D.J., Kaeppler, K.E., Hwang, E., Ehlers, M.E., Toigo, R.D., Giesler, J.D., Vassar-Olsen, E.R. and Hanna, A.
Journal of Microscopy and Research Techniques, 2013, 76(12):1240-1249.
Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury
Hanna A, Thompson DL, Hellenbrand DJ, Lee JS, Madura CJ, Wesley MG, Dillon NJ, Sharma T, Enright CJ, Murphy WL
Journal of Neuroscience Research 2016, 94:645-652.
Treating spinal cord injury via sustained drug delivery from calcium phosphate coatings.
Hellenbrand DJ, and Hanna A
Neural Regeneration Research, 2016 11(8):1236-1237.
Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts
Hellenbrand DJ, Kaeppler KE, Ehlers ME, Thompson CD, Zurko JC, Buchholz MM, Springer AR, Thompson DL, Ibrahim RK, and Hanna AS.
Neurological Research, 2016, 38:12, 1094-1101.
The Effects of Glial Cell Line-Derived Neurotrophic Factor After Spinal Cord Injury.
Rosich K, Hanna B, Ibrahim RK, Hellenbrand DJ, and Hanna AS.
Journal of Neurotrauma, 2017, 34(24): 3311-3325.
Glial cell line-derived neurotrophic factor as a treatment after spinal cord injury.
Ortmann SD and Hellenbrand DJ
Neural Regeneration Research 2018;13:1733-4
Differences in neuroplasticity after spinal cord injury in varying animal models and humans.
Filipp ME, Travis BJ, Henry SS, Idzikowski EC, Magnuson SA, Loh MYF, Hellenbrand DJ, and Hanna AS.
Neural Regeneration Research 2019, 14(1):7-19.