Cerebrolysin Reduces Astrogliosis and Axonal Injury and Enhances Neurogenesis in Rats After Closed Head Injury
| Autor: | Ye Xiong, Talan Zhang, Hemma Brandstaetter, Yi Zhang, Asim Mahmood, Edith Doppler, Michael Chopp, Mei Lu, Zheng Gang Zhang, Yanlu Zhang, Li Zhang, Stefan Winter |
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| Rok vydání: | 2018 |
| Předmět: |
Male
030506 rehabilitation Neuroprotection 03 medical and health sciences chemistry.chemical_compound Random Allocation 0302 clinical medicine Head Injuries Closed Neuroplasticity medicine Animals Amino Acids Rats Wistar Neuroinflammation Brain Concussion biology Dose-Response Relationship Drug business.industry Neurogenesis General Medicine medicine.disease Astrogliosis Rats Disease Models Animal Neuroprotective Agents chemistry Cerebrolysin Closed head injury biology.protein 0305 other medical science business Neuroscience 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Neurorehabilitation and neural repair. 33(1) |
| ISSN: | 1552-6844 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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