1 Henry Ford Hospital, Detroit, MI, USA.
2 Oakland University, Rochester, MI, USA.
Neurorehabil Neural Repair. 2019 Jan;33(1):15-26. doi: 10.1177/1545968318809916. Epub 2018 Nov 30.
Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that cerebrolysin significantly improves functional recovery in rats after mild traumatic brain injury (mTBI).
To determine histological outcomes associated with therapeutic effects of cerebrolysin on functional recovery after TBI.
In this prospective, randomized, blinded, and placebo-controlled study, adult Wistar rats with mild TBI induced by a closed head impact were randomly assigned to one of the cerebrolysin dose groups (0.8, 2.5, 7.5 mL/kg) or placebo, which were administered 4 hours after TBI and then daily for 10 consecutive days. Functional tests assessed cognitive, behavioral, motor, and neurological performance. Study end point was day 90 after TBI. Brains were processed for histological tissue analyses of astrogliosis, axonal injury, and neurogenesis.
Compared with placebo, cerebrolysin significantly reduced amyloid precursor protein accumulation, astrogliosis, and axonal damage in various brain regions and increased the number of neuroblasts and neurogenesis in the dentate gyrus. There was a significant dose effect of cerebrolysin on functional outcomes at 3 months after injury compared with saline treatment. Cerebrolysin at a dose of ⩾0.8 mL/kg significantly improved cognitive function, whereas at a dose of ⩾2.5 mL/kg, cerebrolysin also significantly improved sensorimotor function at various time points. There were significant correlations between multiple histological and functional outcomes 90 days after mTBI.
Our findings demonstrate that cerebrolysin reduces astrogliosis and axonal injury and promotes neurogenesis, which may contribute to improved functional recovery in rats with mTBI.
脑活素是一种具有神经保护和神经营养特性的神经肽制剂。我们之前的研究表明，脑活素可显著改善轻度创伤性脑损伤（mTBI）后大鼠的功能恢复。
确定脑活素对 TBI 后功能恢复的治疗效果相关的组织学结果。
在这项前瞻性、随机、盲法、安慰剂对照研究中，通过闭合性头部撞击诱导轻度 TBI 的成年 Wistar 大鼠被随机分配到脑活素剂量组（0.8、2.5、7.5 mL/kg）或安慰剂组之一，在 TBI 后 4 小时给予，并连续 10 天每天给予一次。功能测试评估认知、行为、运动和神经功能表现。研究终点为 TBI 后第 90 天。对大脑进行组织学分析，以评估星形胶质增生、轴突损伤和神经发生。
与安慰剂相比，脑活素可显著减少不同脑区的淀粉样前体蛋白积累、星形胶质增生和轴突损伤，并增加齿状回的神经前体细胞和神经发生数量。与盐水治疗相比，脑活素在损伤后 3 个月对功能结果有显著的剂量效应。脑活素剂量 ⩾0.8 mL/kg 可显著改善认知功能，而剂量 ⩾2.5 mL/kg 也可显著改善各时间点的感觉运动功能。mTBI 90 天后，多个组织学和功能结果之间存在显著相关性。
我们的研究结果表明，脑活素可减少星形胶质增生和轴突损伤，并促进神经发生，这可能有助于改善 mTBI 大鼠的功能恢复。
