Cerebrolysin dose-dependently improves neurological outcome in rats after acute stroke: A prospective, randomized, blinded, and placebo-controlled study

Journal of Neurosurgery

et al. 2018

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OBJECTIVE Cerebrolysin is a neuropeptide preparation that mimics the properties of neurotrophic factors and has had beneficial effects in the treatment of neurodegenerative diseases, stroke, and traumatic brain injury (TBI). To further evaluate treatment schemes, the authors assessed the dose-response of Cerebrolysin on functional improvement in a rat model of mild TBI (mTBI). METHODS This dose-response study was a prospective, randomized, blinded, and placebo-controlled preclinical experiment. Male Wistar adult rats, subjected to mTBI induced by a closed head impact, were treated randomly with 0 (saline as placebo), 0.8, 2.5, or 7.5 ml/kg of Cerebrolysin 4 hours after mTBI and daily for a total of 10 consecutive days. A battery of cognitive and sensorimotor functional tests was performed over 90 days. RESULTS The primary outcome was functional improvement over the 90 days; animal weight and death were the secondary and safety outcomes, respectively. A significant (p < 0.001) dose effect of Cerebrolysin on cognitive recovery 3 months after injury was found. Cerebrolysin at a dose of ≥ 0.8 ml/kg significantly (p < 0.001) improved cognitive outcome. The higher dose (7.5 ml/kg) resulted in significantly better cognitive recovery than the lowest doses (0.8 ml/kg) but not relative to the 2.5-ml/kg dose. Cerebrolysin at a dose of 2.5 or 7.5 ml/kg also caused different onset times of significant improvement in sensorimotor function. No differences in body weight or mortality rate among the groups were found. CONCLUSIONS This preclinical randomized, placebo-controlled, and blinded study with a clinically relevant treatment scheme revealed that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after mTBI and then once daily for a total of 10 consecutive days, improved functional outcomes 3 months after injury. A dose of 2.5 ml/kg is likely an optimal dose for the treatment of experimental mTBI.

Section: Discussionmentioning

confidence: 96%

“…Cerebrolysin were selected based on our previous studies in rats with experimental stroke 59 or mTBI. 60 The study design, surgeries, preparation of study medication, treatment, data collection, and analysis were each performed by different and independent members of the Henry Ford Hospital.…”

mentioning

confidence: 99%

Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury

Zhang¹,

Chopp

Journal of Neurosurgery

et al. 2018

Self Cite

“…The drug doses were chosen based on our previous studies in TBI 18 and stroke. 17 Treatment with study drug was initiated 4 hours after injury and was administered intraperitoneally once daily for 10 consecutive days. Study medication was prepared by a designated investigator (who was not involved in any other part of this study) according to animal body weight, 1 day prior to treatment based on the randomization scheme.…”

Section: Animal Groups and Treatmentmentioning

confidence: 99%

“…12 Besides these protective effects, cerebrolysin promotes neurogenesis in animal models of AD, 13 stroke, 14,15 and TBI. 16,17 Cerebrolysin increases neuronal survival in the hippocampus, preserves axonal integrity in the striatum, enhances vascular patency and integrity after moderate TBI, 18 and reduces APP levels and astrogliosis in rats after mTBI. 16 Collectively, these multiple beneficial effects resulting from cerebrolysin treatment may in concert contribute to improvement of neurological outcome after brain injury.…”

Section: Introductionmentioning

confidence: 99%

Cerebrolysin Reduces Astrogliosis and Axonal Injury and Enhances Neurogenesis in Rats After Closed Head Injury

Chopp

Neurorehabil Neural Repair

et al. 2018

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Background. 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). Objective. To determine histological outcomes associated with therapeutic effects of cerebrolysin on functional recovery after TBI. Methods. 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. Results. 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. Conclusions. Our findings demonstrate that cerebrolysin reduces astrogliosis and axonal injury and promotes neurogenesis, which may contribute to improved functional recovery in rats with mTBI.

Z. nevrol. psikhiatr. im. S.S. Korsakova

“…Под влиянием препарата активируются нейрогенез, синаптогенез и олигодендрогенез [55]. Введение Церебролизина при фокаль-ной ишемии приводит к снижению объема поврежденной мозговой ткани [56,57], что способствует формированию менее выраженной постинсультной симптоматики.…”

Section: применение церебролизинаunclassified

Cognitive rehabilitation of patients with focal brain damage

Боголепова¹,

Левин²

2020

Резюме Одной из важных проблем современной неврологии являются когнитивные нарушения, возникшие вследствие очагового поражения головного мозга при инсульте и черепно-мозговой травме. Когнитивный дефицит оказывает негативное влияние на качество жизни больного и его окружения, в большой мере препятствуя возможности возвращения к полноценному социальному и профессиональному восстановлению. Таким больным необходимо проведение комплексного реабилитационного лечения, включающего когнитивную реабилитацию, двигательную реабилитацию и медикаментозную коррекцию. Обсуждается применение Церебролизина, эффективность которого у больных после инсульта и черепно-мозговой травмы подтверждена многочисленными исследованиями.