title: Cerebrolysin improves cognitive performance in rats after mild traumatic brain injury.
abstract: OBJECTIVE
  Long-term memory deficits occur after mild traumatic brain injuries (mTBIs), and effective treatment modalities are currently unavailable. Cerebrolysin, a peptide preparation mimicking the action of neurotrophic factors, has beneficial effects on neurodegenerative diseases and brain injuries. The present study investigated the long-term effects of Cerebrolysin treatment on cognitive function in rats after mTBI.
  
  
  METHODS
  Rats subjected to closed-head mTBI were treated with saline (n = 11) or Cerebrolysin (2.5 ml/kg, n = 11) starting 24 hours after injury and then daily for 28 days. Sham animals underwent surgery without injury (n = 8). To evaluate cognitive function, the modified Morris water maze (MWM) test and a social odor-based novelty recognition task were performed after mTBI. All rats were killed on Day 90 after mTBI, and brain sections were immunostained for histological analyses of amyloid precursor protein (APP), astrogliosis, neuroblasts, and neurogenesis.
  
  
  RESULTS
  Mild TBI caused long-lasting cognitive memory deficits in the MWM and social odor recognition tests up to 90 days after injury. Compared with saline treatment, Cerebrolysin treatment significantly improved both long-term spatial learning and memory in the MWM test and nonspatial recognition memory in the social odor recognition task up to 90 days after mTBI (p < 0.05). Cerebrolysin significantly increased the number of neuroblasts and promoted neurogenesis in the dentate gyrus, and it reduced APP levels and astrogliosis in the corpus callosum, cortex, dentate gyrus, CA1, and CA3 regions (p < 0.05).
  
  
  CONCLUSIONS
  These results indicate that Cerebrolysin treatment of mTBI improves long-term cognitive function, and this improvement may be partially related to decreased brain APP accumulation and astrogliosis as well as increased neuroblasts and neurogenesis.
authors.affiliation: Departments of 1 Neurosurgery and.
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Yuling
authors.initials: Y
authors.lastname: Meng
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Edith
authors.initials: E
authors.lastname: Doppler
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.forename: Timothy
authors.initials: T
authors.lastname: Schallert
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000054:Acceleration; D000596:Amino Acids / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D002452:Cell Count; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D000089662:Doublecortin Protein; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012919:Social Behavior
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; C006952:cerebrolysin
keywords: APP = amyloid precursor protein; BSA = bovine serum albumin; BrdU = 5′-bromo-2′-deoxyuridine; Cerebrolysin; DCX = doublecortin; GFAP = glial fibrillary acidic protein; MWM = Morris water maze; NeuN = neuronal nuclei; PBS = phosphate-buffered saline; TBI = traumatic brain injury; amyloid precursor protein; cognitive function; mTBI = mild TBI; mild closed head injury; neuroblast; neurogenesis; sAPPα = soluble α form of APP; traumatic brain injury