title: Protease activated receptor-1 and brain edema formation in glioma models.
abstract: OBJECTIVE
  Our previous studies showed that thrombin contributes to brain edema in gliomas. The present study investigated the role of a thrombin receptor, protease activated receptor-1 (PAR-1), in edema formation in glioma models.
  
  
  METHODS
  These experiments were performed in Fischer 344 rats, PAR-1 knockout mice, and wild-type C57BL/6 mice controls. F98 glioma cells were infused into the right caudate. Animals were euthanized and the brains were used for measurements of brain edema and PAR-1 expression.
  
  
  RESULTS
  In rats, implantation of glioma cells resulted in significant brain edema in the ipsilateral hemisphere (82.6 ± ;1.4 vs. 78.1 ± 0.9 % in the contralateral hemisphere, p < 0.01). By Western blot analysis and RT-PCR, we found that both protein and mRNA levels of PAR-1 were upregulated in the glioma (p < 0.01). In mice, implantation of glioma cells also caused brain edema in the ipsilateral hemisphere (p < 0.05). Glioma-induced brain edema was less in PAR-1 knockout mice (day 12: 79.4 ;± 1.3 vs. 81.5 ± 1.1 % in the wild-type mice, p < ;0.05).
  
  
  CONCLUSIONS
  PAR-1 plays a role in glioma-induced brain edema. Clarification of the role of PAR-1 in edema formation should help to develop new therapeutic strategies for gliomas.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Ye
authors.initials: Y
authors.lastname: Gong
authors.forename: Richard
authors.initials: R
authors.lastname: Keep
authors.forename: Karin
authors.initials: K
authors.lastname: Muraszko
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000209:etiology*; D001932:Brain Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation / Q000379:methods; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D018709:Statistics, Nonparametric
chemical_list: D011494:Protein Kinases; C036447:protease activated kinase I