Injury-Transplantation Interval-Dependent Amelioration of Axonal Degeneration and Motor Deficit in Rats with Penetrating Traumatic Brain Injury

• Published in: Neurotrauma reports Vol. 4; no. 1; pp. 225 - 235
• Main Authors: Andreu, MaryLourdes, Sanchez, Liz M Quesada, Spurlock, Markus S, Hu, Zhen, Mahavadi, Anil, Powell, Henry R, Lujan, Maria M, Nodal, Samuel, Cera, Melissa, Ciocca, Isabella, Bullock, Ross, Gajavelli, Shyam
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc., publishers 01.04.2023; Mary Ann Liebert
• Subjects: human neural stem cells; mitigation of secondary injury; Original; Original Article; penetrating traumatic brain injury; human neural stem cells; penetrating traumatic brain injury; mitigation of secondary injury
• ISSN: 2689-288X; 2689-288X
• DOI: 10.1089/neur.2022.0087

Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial–grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation.