Abstract
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 T2-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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Acknowledgements
We thank Dr. Allison Neely at the Laboratory Animal Resources facility at the University of Kansas Medical Center for performing animal necropsies.
Funding
This study was supported by funding from the National Institutes of Health (R21 NS091920 to Dr. Janna Harris and P30 AG035982 to the University of Kansas Alzheimer’s Disease Center) and a KUMC Lied Basic Science grant awarded to Dr. Harris. The Hoglund Brain Imaging Center is supported by Forrest and Sally Hoglund and the University of Kansas School of Medicine. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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Gupte, R., Christian, S., Keselman, P. et al. Evaluation of taurine neuroprotection in aged rats with traumatic brain injury. Brain Imaging and Behavior 13, 461–471 (2019). https://doi.org/10.1007/s11682-018-9865-5
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DOI: https://doi.org/10.1007/s11682-018-9865-5