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
Mineral coated microparticles delivering Interleukin-4, Interleukin-10, and Interleukin-13 reduce inflammation and improve function after spinal cord injury in a rat
Hellenbrand DJ, Lee JS, Mickelson EJ, Baer MC, Ott EL, Martinson NR, Celeen MR, Hilger KH, Nielsen BE, Jacobs AN, Mishra RR, Hurley SA, Murphy WL, Hanna AS.
Exp Neurol. 2025 Feb 4;386:115179
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
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
Brachial Plexus Anatomy of Sprague Dawley Rat Compared to Human.
Jacobs AN, Bolstad LJ, Martinson N, Mickelson E, Ceelen MR, Lefebvre OR, Klein RR, Hellenbrand DJ, Hanna AS.
J Brachial Plex Peripher Nerve Inj. 2025 May 29;20(1):e31-e40.
Comparison of nylon, vicryl, and fibrin glue for nerve grafting in rats.
Hanna AS, Mickelson E, Omar AH, Baer M, Sveum J, Marti T, Mishra R, Trudrung M, Hutchinson J, Attaluri P, Jacobs A, Ott E, Martinson N, Jones J, Hellenbrand D.
Neurol Res. 2024 Oct;46(10):972-981
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
Background
One of Dr. Hanna’s goals is to educate and teach up and new coming surgeons. He has recently published two books to aid in understanding the operative exposures of nerves and a case based approached book that addresses a knowledge deficit in nerves amongst neurosurgeons. He has also performed a study using cadavers to correct a longstanding misconception of the brachial plexus arrangement and to design a new more accurate diagram. In addition, he has conducted another anatomical study defining the lateral femoral cutaneous nerve canal and designed a new technique to find the nerve during surgery using ultrasound guided wire placement. In clinic, he treats several severe nerve injuries and these patients are the driving force behind his research. We need methods to improve the amount of function lost in patients with nerve injuries, which will significantly increase their quality of life.
Most Relevant Publications
Nerves: Anatomy, Exposures, and Techniques (Second Edition)
Hanna AS.
New York. Springer International Publishing. 2025
Rib-Sparing Anterior Scalenectomy Versus First Rib Resection for the Treatment of Thoracic Outlet Syndrome.
Ansari D, Maghrabi H, Eslami A, Hanna AS.
Oper Neurosurg. Published online May 21, 2025.
Anatomical Relationships of the Sciatic Nerve and Pudendal Nerve to the Ischial Spine as They Exit the Greater Sciatic Foramen.
Hanna AS, Staniszewski TM, Omar AH, Guevara-Moriones N, Moscote-Salazar LR, Hilger KH, Hellebrand DJ.
World Neurosurg. 2024 Mar;183:e564-e570.
Anatomical Proximity Between Sciatic Nerve and Ischial Spine and its Relationship to the Development of Deep Gluteal Pain Syndrome
Hanna AS, Schmidt BT, Kanarek AA, Hilger KH, Blankenbaker DG, Medhat H, Moscote-Salazar LR, Hellenbrand DJ.
World Neurosurg. 2024 Aug;188:e367-e375
The SPA arrangement of the branches of the upper trunk of the brachial plexus: a correction of a longstanding misconception and a new diagram of the brachial plexus
Hanna AS.
J Neurosurg. 2016 Aug;125(2):350-4
For a complete list of publications, see Google Scholar Link:
Amgad Hanna Google Scholar
Recent and Current Funding Agencies
- National Institutes of Health R01NS136564: (3/15/2024 – 12/31/2027)
- Niall’s Foundation Research Grant: (10/1/2023 – 12/1/2024)
- National Institutes of Health 1R56NS117935: (5/1/2021 – 4/30/2022)
- Fraternal Order of Eagles Foundation: (11/1/2015 – 11/1/2016)
- Bryon Riesch Paralysis Foundation Grant: (4/1/2014 – 8/1/2015)
- Grateful Patient: (2015)
- Bryon Riesch Paralysis Foundation Grant: (4/1/2012 – 4/1/2013)
A special thanks to all the funding agencies!
