Abstract Background Traumatic brain injuries (TBIs) are a leading cause of death and disability, with penetrating TBIs the most lethal form. While no TBI treatments currently exist, ongoing investigations are developing biomaterial scaffolds and cellular therapies to improve the poor outcomes of this disease. Objective This pilot study established a TBI rat model that maintains focal damage to the cerebral cortex while manually disrupting the blood-brain barrier (BBB). BBB-disrupting injuries require different management from others, allowing us to develop a specific, therapeutic treatment for this type of injury. We hypothesized that our method of BBB disruption would indicate behavioral, physical, and histological evidence of a TBI. Our TBI model will also create a cranial opening in which we can ensure surgical feasibility of implantation of a scaffold. We hypothesized that the implantation of a Food and Drug Administration–approved synthetic polymer, poly(lactic-co-glycolic) acid (PLGA), and a carbon-based nanomaterial, reduced graphene oxide (rGO), would not show evidence of foreign body rejection 30 days after surgery. Methods Sprague Dawley rats (N=4) underwent stereotaxic surgery with a 5-mm craniotomy. The dura and brain tissue were disrupted using a beaver blade. The PLGA/rGO scaffold was gently placed onto the brain tissue. Neurological function (including body condition, breathing, spontaneous behavior, handling reaction) was evaluated for the first 3 days, then weekly throughout the 30-day study. At 30 days, the brains were dissected, paraffin embedded, and sectioned for H&E and Prussian blue staining, and immunohistochemistry (IHC) using glial fibrillary acidic protein, neuronal nuclei (NeuN), von Willebrand factor, neurofilament light chain, ionized calcium-binding adapter molecule 1, and CD68 markers. Data were expressed as means and SDs, and 2-tailed t tests were used to determine statistical significance ( P ≤.05). Results Neurological function assessments indicated no change in rat behavior and normal wound healing over the 30-day study. H&E and Prussian blue staining indicated mild leptomeningeal thickening and evidence of hemosiderin in 3 rats. One rat had foreign body giant cells and an abscess around the implanted material, with evidence of more severe leptomeningeal thickening and hemosiderin. IHC indicated normal anatomic structures with no changes in 5 of the 6 markers 30 days after surgery. NeuN significantly decreased in expression, from 9.65% to 4.56% in area, for all 4 rats ( P =.02). Conclusions While there was no behavioral or symptomatic evidence of TBI, histology showed evidence of mild, focal TBI in 3 of the 4 rats and evidence of a foreign body response and a severe, focal TBI in 1 rat. This pilot study provides a basis for future studies to perform IHC at earlier time points to confirm additional biomarkers. Future studies will also implant a scaffold that is more mechanically aligned with the brain tissue to further evaluate the biocompatibility of graphene nanoparticles in brain tissue and the effectiveness of a therapeutic scaffold.
Harley‐Troxell et al. (Fri,) studied this question.