Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Brain Imaging Behav. 2019 Apr;13(2):461-471. doi: 10.1007/s11682-018-9865-5.
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.
尽管 65 岁以上的创伤性脑损伤 (TBI) 患者的住院率和死亡率较高,但在药物开发研究中,老年患者的代表性仍然不足。与年轻成年人相比,老年个体的预后较差可能归因于加剧的损伤机制,包括氧化应激、炎症、血脑屏障破坏和生物能量功能障碍。因此,多效治疗是神经保护的有吸引力的候选物。牛磺酸是一种内源性氨基酸,具有抗氧化、抗炎、抗细胞凋亡、渗透调节和神经调节作用,在 TBI 的成年大鼠中具有神经保护作用。然而,其在老年大脑中的作用尚未得到评估。我们使老年雄性大鼠接受单侧皮质感觉运动区的控制性皮质撞击损伤,并将它们随机分为四组治疗:盐水或 25mg/kg、50mg/kg 或 200mg/kg 腹腔内牛磺酸。治疗在损伤后 20 分钟内进行,每天一次,持续 7 天。我们在 TBI 后第 1-14 天评估感觉运动功能,并在第 14 天使用 T 加权磁共振成像评估组织损失。在整个研究过程中,实验者对治疗组保持盲态。我们没有观察到牛磺酸对 TBI 后老年大鼠的功能障碍或组织损失有神经保护作用。这些在老年大鼠中的发现与以前关于牛磺酸在年轻动物中的神经保护作用的报告相反。年龄是 TBI 药物开发研究的一个重要变量,需要进一步研究以更好地了解衰老如何影响牛磺酸神经保护的机制。