A Prospective, Randomized, Blinded, and Placebo-Controlled Study of Cerebrolysin Effect on Long-Term Functional and Histological Outcomes in Rats with Traumatic Brain Injury

Background and aims: Our previous study identified an optimal dose of Cerebrolysin as 2.5ml/kg for treatment of mild traumatic brain injury (TBI) when administered 4h after injury. The present study was designed to investigate the effects of Cerebrolysin at this dose on functional and histological outcomes in rats subjected to moderate TBI. Methods: In this prospective, randomized, blinded, and placebo-controlled preclinical study, male adult Wistar rats, subjected to TBI induced by impact acceleration, were randomly treated with either placebo (saline, n=13) or Cerebrolysin at the dose of 2.5ml/kg (n=13), intraperitoneally administered daily for 10 days, starting at 4h after TBI. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points and sacrificed at 90 days after TBI for histological analyses. Results: Compared to the placebo, Cerebrolysin significantly increased neurogenesis, reduced amyloid precursor protein accumulation, astrogliosis and axonal damage and reduced neuronal cell loss in the hippocampus (p\u3c0.05). Sensory motor function was significantly improved in the Cerebrolysin group compared to controls from 1 day to 3 months after injury (p\u3c0.05). Cerebrolysin significantly improved long-term (up to 3 months) cognitive functional recovery measured by the Morris Water Maze, Odor Recognition, Social Interaction, and Novel Object Recognition tests. There were significant correlations between multiple histological and functional outcomes 90 days after TBI, as detected by Pearson partial correlation analyses. Conclusion: Our data demonstrate that Cerebrolysin significantly improves functional outcome after moderate TBI in rat, and that functional outcomes are significantly correlated with histological indices of plasticity