title: Effect of thrombin preconditioning on migration of subventricular zone-derived cells after intracerebral hemorrhage in rats.
abstract: OBJECTIVE
  To investigate the effect of thrombin preconditioning (TPC) on the intracerebral hemorrhage (ICH)-induced proliferation, migration, and function of subventriclular zone (SVZ) cells and to find new strategies that enhance endogenous neurogenesis after ICH.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into 3 groups (ICH, TPC, and control group). Rats of each group were randomly divided into 5 subgroups (3-d, 7-d, 14-d, 21-d, and 28-d subgroup). ICH was caused by intrastrial stereotactic administration of collagenase type IV. Brdu was used to label newborn SVZ cells. Organotypic brain slices were cultured to dynamically observe the migration of SVZ cells at living brain tissue. Migration of Dil-labeled SVZ cells in living brain slices was traced by time-lapse microscopy. To assess whether SVZ cells migrating to injured striatum had the ability to form synapses with other cells, brain slices from each group were double immunolabeled with Brdu and synapsin I.
  
  
  RESULTS
  The number of Brdu-positive cells markedly increased in the ipsilateral SVZ and striatum 3 days after TPC, peaked at 14 days (P < 0.01), continued to 21 days, and then gradually decreased at 28 days with significant difference compared to the ICH group at each time point (P < 0.01). Migration of Dil-labeled SVZ cells in brain slices in each group was observed and imaged during a 12-h period. Dil-labeled SVZ cells in the TPC group were observed to migrate laterally toward striatum with time with a faster velocity compared to the ICH group (P < 0.01). Our study also demonstrated that TPC induced strong colocalization of Brdu and synapsin I in the ipsilateral striatum between 3 and 28 days after injury.TPC made colocalization of Brdu and synapsin I appear earlier and continue for a longer time compared to the ICH group.
  
  
  CONCLUSIONS
  Our results demonstrated that TPC could promote proliferation, migration, and function of SVZ cells after ICH, which may provide a new idea for enhancing endogenous neurogenesis and developing new therapeutic strategies against ICH-induced brain injury.
authors.affiliation: a Department of Neurology , Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Guan
authors.affiliation: a Department of Neurology , Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a Department of Neurology , Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: a Department of Neurology , Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: a Department of Neurology , Renmin Hospital of Wuhan University , Wuhan , China.
authors.forename: Zuneng
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology*; D002552:Cerebral Ventricles / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D016704:Synapsins; D013917:Thrombin; D001973:Bromodeoxyuridine
keywords: Intracerebral hemorrhage; Subventricular zone; Thrombin preconditioning