Transplant Location Dependent Mitigation Of Traumatic Brain Injury Pathology and Motor Deficit in Rats

Motor Deficit in Rats Liz Quesada*, Markus Spurlock, Stephanie W. Lee, Julia Janecki, Zhen Hu, Karla N. Rivera, Anil Mahavadi, Ganesh R. Gajavelli, Deborah Shear, Shyam Gajavelli & Ross Bullock Penetrating traumatic brain injury(PTBI) is common in the USA and worldwide, outcome remains poor in survivors. In the absence of “neuroprotective” therapies, progressive secondary tissue loss after PTBI underlies disability among survivors. This study tests transplantation of human neural stem cells (hNSCs) as a treatment to mitigate lesion in penetrating ballistic-like brain injury (PBBI), a rat PTBI model. One-week post PBBI male Sprague Dawley rats (710/group) were randomized to: (1) injured treated with vehicle (media, no cells), (2) uninjured (sham+hNSCs), two PBBI groups (PBBI+hNSC) either (3) into surrounding (peri) or (4) within lesion core(intra), one million cells were stereotactically microinjected into brains of immunosuppressed group 2-4. Motor function was assessed on grid walk prior to euthanasia at 12 weeks post-transplantation. Lesion size, axonal injury was quantitated with Matlab based scripts of brain sections stained with histochemical stains. Lesion size and remote secondary axotomy were significantly reduced in transplant groups. Engraftment or neuronal differentiation did not differ between groups 3 and 4, despite being higher than in sham. On the grid walk test, sham animals had fewer foot faults than vehicle group as expected. Compared to vehicle, groups 3 and 4 had significantly reduced foot faults but still significantly higher than control.