Despite higher rates of hospitalization and mortality following traumatic brain injury (TBI) in patients over 65 years old, older patients remain underrepresented in drug development studies. Worse outcomes in older individuals compared to younger adults could be attributed to exacerbated injury mechanisms including oxidative stress, inflammation, blood-brain barrier disruption, and bioenergetic dysfunction. Accordingly, pleiotropic treatments are attractive candidates for neuroprotection. Taurine, an endogenous amino acid with antioxidant, anti-inflammatory, anti-apoptotic, osmolytic, and neuromodulator effects, is neuroprotective in adult rats with TBI. However, its effects in the aged brain have not been evaluated. We subjected aged male rats to a unilateral controlled cortical impact injury to the sensorimotor cortex, and randomized them into four treatment groups: saline or 25 mg/kg, 50 mg/kg, or 200 mg/kg i.p. taurine. Treatments were administered 20 min post-injury and daily for 7 days. We assessed sensorimotor function on post-TBI days 1-14 and tissue loss on day 14 using T-weighted magnetic resonance imaging. Experimenters were blinded to the treatment group for the duration of the study. We did not observe neuroprotective effects of taurine on functional impairment or tissue loss in aged rats after TBI. These findings in aged rats are in contrast to previous reports of taurine neuroprotection in younger animals. Advanced age is an important variable for drug development studies in TBI, and further research is required to better understand how aging may influence mechanisms of taurine neuroprotection.

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Background Age is the main risk factor for many neurodegenerative disorders including Alzheimer’s disease (AD). One hallmark of brain aging is mitochondrial impairment resulting in bioenergetic dysfunction. Therefore, limiting age‐related decline in mitochondrial function may be an attractive therapeutic strategy to mitigate the risk of AD. Oxaloacetate (OAA) is a metabolic intermediate in the TCA cycle, gluconeogenesis, and amino acid biosynthesis. Treatment with OAA has been shown to enhance neuronal bioenergetics, neurogenesis, and mitochondrial biogenesis in young adult mice, but its effects in aged subjects are unknown. We sought to determine whether OAA treatment in aged rats can alter brain metabolism and mitochondrial function. Method In aged male F344 rats (20‐22 months) we used in vivo proton magnetic resonance spectroscopy (1H‐MRS) to obtain baseline neurometabolic readings from two regions of interest: Ctx+ (cortex and subcortical tissue) and Hipp (hippocampus and dorsal striatum). We then treated rats with 1 g/kg/day i.p. OAA (n=14) or vehicle (n=14) for 7 days, followed by post‐treatment 1H‐MRS scans. On day 8 we used an Oxygraph‐2k to compare brain mitochondrial respiration in the OAA vs. vehicle‐treated groups. Result OAA treatment significantly increased levels of N‐acetylaspartate, glutamate, aspartate, phosphocreatine, lactate, alanine, and ascorbate in a region‐dependent manner. No significant differences were observed in mitochondrial respiratory flux between the OAA and vehicle‐treated groups. Conclusion After 1 week of treatment with OAA, aged rats showed changes in brain metabolites linked with bioenergetic function but did not show significant differences in the kinetics or capacity of brain mitochondrial respiration. These findings diverge from previously reported effects of OAA in younger adult mice, highlighting the critical importance of testing novel AD therapies across a range of ages.