Amgad S. Hanna Lab

Background

After spinal cord injury (SCI) there is immediate mechanical damage that causes cell death and breakdown of the blood-spinal cord barrier. This primary insult sets off a secondary injury cascade consisting of prolonged inflammation and an extensive infiltration of peripherally derived immune cells, which leads to additional neural damage. Initially astrocytes migrate to the lesion, proliferate and aid in the tissue repair process after SCI. However, astrocytes eventually become scar-forming astrocytes forming a glial scar, which encapsulates the entire lesion. Although the glial scar protects the remaining intact spinal cord from further damage, the dense glial scar has been shown to inhibit axon regeneration. Our lab is investigating treatments to reduce secondary damage in the acute phase and treatments to promote regeneration in chronic SCI. Specifically, the treatments involve methods to optimize the delivery of biologically active therapeutic molecules using mineral coated microparticles (MCMs).

Reducing Secondary Damage after SCI

To reduce inflammation after SCI, we are investigating the use of anti-inflammatory cytokines, which possess the capability to shift macrophages to an anti-inflammatory state, reducing the release of pro-inflammatory cytokines, and thus reducing the exacerbated amount of infiltrating immune cells. Although anti-inflammatory cytokines have been known for decades, anti-inflammatory cytokines have a short half-life and are unable to cross the blood-spinal cord barrier, which limits their therapeutic potential. MCMs stabilize cytokines, minimizing cytokine denaturation and allow for the release of biologically active cytokines for an extended timeframe. Our current studies involve using MCMs delivering multiple anti-inflammatory cytokines for at least two weeks after SCI, to reduce inflammation and improve function below the injury.

Promoting Regeneration after SCI

To promote regeneration in chronic SCI, we are investigating methods to reduce inhibitory molecules in the glial scar and growth factors to promote axon regeneration. Chondroitinase ABC is an enzyme capable of degrading chondroitin sulfate proteoglycan, the predominant molecule shown to inhibit axon regeneration in the glial scar. However, poor protein stability remains a challenge in its therapeutic use. Previous studies have shown that MCMs delivering mRNA efficiently transfect cells to upregulate proteins of interest and sequester the upregulated protein on the MCM for prolonged delivery of the therapeutic protein. Our current studies involve using MCM-mediated transfection of Chondroitinase ABC-encoding mRNA to digest inhibitory molecules in the glial scar along with delivery of growth factors to enhance axon regeneration.

Most Relevant Publications

The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation
Daniel J. Hellenbrand, Charles M. Quinn, Zachariah J. Piper, Ryan T. Elder, Raveena R. Mishra, Taylor L. Marti, Phoebe M. Omuro, Rylie M. Roddick, Jae Sung Lee, William L. Murphy, Amgad S. Hanna
Neural Regeneration Research 2024

A localized materials-based strategy to non-virally deliver Chondroitinase ABC mRNA improves hindlimb function in a rat spinal cord injury model
Andrew S. Khalil, Daniel Hellenbrand, Kaitlyn Reichl, Jennifer Umhoefer, Mallory Filipp, Joshua Choe, Amgad Hanna, William L. Murphy
Adv. Healthcare Mater. 2022, 11, 2200206

Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration
Daniel J. Hellenbrand, Charles M. Quinn, Zachariah J. Piper, Carolyn N. Morehouse, Jordyn A. Fixel and
Amgad S. Hanna
Journal of Neuroinflammation (2021) 18:284

Sustained interleukin-10 delivery reduces inflammation and improves motor function after spinal cord injury
Hellenbrand DJ, Reichl KA, Travis BJ, Filipp ME, Khalil AS, Pulito DJ, Gavigan AV, Maginot ER, Arnold MT, Adler AG, Murphy WL, and Hanna AS
Journal of Neuroinflammation 2019, 16:93

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

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

For a complete list of publications, see Google Scholar Link:
Amgad Hanna Google Scholar

Enhancing Axon Regeneration after Nerve Injury

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.

Brachial Plexus Injury

Brachial plexus injury (BPI) occurs when the brachial plexus is compressed, stretched, or avulsed. Although rodents are commonly used to study BPI, these models poorly mimic human BPI due to the discrepancy in size. Our lab is working to develop an animal model to more closely mimic human BPI to aid in the development of treatments for BPI

Most Relevant Publications

Gait analysis in swine, sheep, and goats after neurologic injury: a literature review
Sveum JW, Mishra RR, Marti TL, Jones JM, Hellenbrand DJ, Hanna AS.
Neural Regeneration Research. 2023, 18(9):1917-1924.

Brachial plexus anatomy in the miniature swine as compared to human
Amgad S Hanna, Daniel J Hellenbrand, Dominic T Schomberg, Shahriar M Salamat, Megan Loh, Lea Wheeler, Barbara Hanna, Burak Ozaydin, Jennifer Meudt, Dhanansayan Shanmuganayagam
Journal of Anatomy. 2022, 240:172–181.

Functional recovery after peripheral nerve injury via sustained growth factor delivery from mineral-coated microparticles
Hellenbrand DJ, Haldeman CL, Lee JS, Gableman AG, Dai EK, Ortmann SD, Gotchy JC, Miller KK, Nowak NC, Murphy WL,, and Hanna AS.
Neural Regeneration Research 2021, 16(5):871-877.

For a complete list of publications, see Google Scholar Link:
Amgad Hanna Google Scholar

Improving Function after Nerve Injury via Sustained Growth Factor Delivery from Mineral Coated Microparticles.
Hellenbrand DJ, Haldeman CL, Lee JS, Gableman AG, Dai EK, Ortmann SD, Gotchy JC, Miller KK, Nowak NC, Murphy WL,, and Hanna AS.
Neural Regeneration Research 2021, 16(5):871-877.

The role of interleukins after spinal cord injury.
Hellenbrand D, Roddick R, Mauney S, Elder R, Morehouse C, Hanna A.
Interleukin. IntechOpen, March 2021.

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.

For a complete list of publications, see Google Scholar Link:

Amgad Hanna Google Scholar