title: Citicoline enhances neuroregenerative processes after experimental stroke in rats.
abstract: OBJECTIVE
  The neuroprotective potential of citicoline in acute ischemic stroke has been shown in many experimental studies and, although the exact mechanisms are still unknown, a clinical Phase III trial is currently underway. Our present study was designed to check whether citicoline also enhances neuroregeneration after experimental stroke.
  
  
  METHODS
  Forty Wistar rats were subjected to photothrombotic stroke and treated either with daily injections of citicoline (100 mg/kg) or vehicle for 10 consecutive days starting 24 hours after ischemia induction. Sensorimotor tests were performed after an adequate training period at Days 1, 10, 21, and 28 after stroke. Then brains were removed and analyzed for infarct size, glial scar formation, neurogenesis, and ligand binding densities of excitatory and inhibitory neurotransmitter receptors.
  
  
  RESULTS
  Animals treated with citicoline showed a significantly better neurological outcome at Days 10, 21, and 28 after ischemia, which could not be attributed to differences in infarct volumes or glial scar formation. However, neurogenesis in the dentate gyrus, subventricular zone, and peri-infarct area was significantly increased by citicoline. Furthermore, enhanced neurological outcome after citicoline treatment was associated with a shift toward excitation in the perilesional cortex.
  
  
  CONCLUSIONS
  Our present data demonstrate that, apart from the well-known neuroprotective effects in acute ischemic stroke, citicoline also possesses a substantial neuroregenerative potential. Thanks to its multimodal effects, easy applicability, and history as a well-tolerated drug, promising possibilities of neurological treatment including chronic stroke open up.
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Diederich
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.forename: Jens
authors.initials: J
authors.lastname: Minnerup
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Schneider
authors.forename: Antje
authors.initials: A
authors.lastname: Schmidt
authors.forename: Elena
authors.initials: E
authors.lastname: Altach
authors.forename: Verena
authors.initials: V
authors.lastname: Eggert
authors.forename: Clemens J
authors.initials: CJ
authors.lastname: Sommer
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
mesh_terms: D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D003566:Cytidine Diphosphate Choline