Traumatic brain injury (TBI) results in the generation of tau. As hyperphosphorylated tau (p-tau) is one of the major consequences of TBI, targeting p-tau in TBI may lead to the development of new therapy. Twenty-five pigs underwent a controlled cortical impact. One hour after TBI, pigs were administered either vehicle (n = 13) or PNT001 (n = 12), a monoclonal antibody for the cis conformer of tau phosphorylated at threonine 231. Plasma biomarkers of neural injury were assessed for 14 days. Diffusion tensor imaging was performed at day 1 and 14 after injury, and these were compared to historical control animals (n = 4). The fractional anisotropy data showed significant white matter injury for groups at 1 day after injury in the corona radiata. At 14 days, the vehicle-treated pigs, but not the PNT001-treated animals, exhibited significant white matter injury compared to sham pigs in the ipsilateral corona radiata. The PNT001-treated pigs had significantly lower levels of plasma glial fibrillary acidic protein (GFAP) at day 2 and day 4. These findings demonstrate a subtle reduction in the areas of white matter injury and biomarkers of neurological injury after treatment with PNT001 following TBI. These findings support additional studies for PNT001 as well as the potential use of this agent in clinical trials in the near future.

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO₂) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO₂ was higher in hyperoxia animals throughout CPB (p < 0.001). There were no differences in cortical glycerol concentration between groups (p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals (p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration (p = 0.48), protein carbonyls (p = 0.74), or reactive oxygen species generation (p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.