title: Antisense oligodeoxynucleotides targeting connexin43 reduce cerebral astrocytosis and edema in a rat model of traumatic brain injury.
abstract: OBJECTIVE
  Brain injury induces an acute increase in the expression of gap junction protein connexin43 (Cx43). It also leads to cerebral edema, probably due to the swelling and proliferation of astrocytes reactive to the injury. Antisense oligodeoxynucleotides (AS-ODN) targeting Cx43 were tested for their ability to reduce reactive astrocytosis and cerebral edema in a rat model of traumatic brain injury (TBI).
  
  
  METHODS
  The brains of experimental animals were intraventricularly injected with these AS-ODNs, while sham rats and normal controls were administered saline in the same way. Controlled cortical impact (CCI) injury was induced in both experimental and sham rats, then the damaged brain tissue was stained for glial fibrillary acidic protein (GFAP) immunofluorescein, measured for water content using the wet-dry weight method, and examined for Cx43 protein expression by western blotting.
  
  
  RESULTS
  The brains of both experimental and sham groups were found to have a higher level of Cx43 expression, higher water content, and more swollen and proliferative astrocytes than the normal controls at 6 hours, 24 hours, and 48 hours post-trauma. But compared with the sham animals, brains of experimental rats showed less Cx43 expression, lower water content, and less swollen and proliferative astrocytes. These two brain-injured groups displayed a similar pattern of changes in these outcomes over the 48-hour time period studied.
  
  
  CONCLUSIONS
  Antisense oligodeoxynucleotides targeting Cx43 reduced reactive astrocytosis and cerebral edema following TBI, indicating that Cx43 might be involved in regulating the water imbalance between brain cells.
authors.affiliation: Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Xu
authors.forename: Yalong
authors.initials: Y
authors.lastname: He
authors.forename: Guitao
authors.initials: G
authors.lastname: Yang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Liao
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Liang
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D018031:Connexin 43 / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018031:Connexin 43; D020319:Oligodeoxyribonucleotides, Antisense