bcl-2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain

Shigetoshi Shimizu, Tetsuya Nagayama, Kun Lin Jin, Li Zhu, J. Eric Loeffert, Simon C. Watkins, Steven H. Graham, Roger P. Simon

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


In the rat, 60 minutes of transient ischemia to the middle cerebral artery results in infarction of the caudate putamen. Ischemic preconditioning with 20 minutes of transient focal ischemia produced tolerance (attenuated infarction volume) to 60 minutes of subsequent focal ischemia administered three days, five days, or seven days later. Western blots from tolerant caudate putamen demonstrated increased bcl-2 expression, maximum at 3 days and persisting through 7 days. Immunocytochemical examination found that bcl-2 was expressed in cells with both neuronal and nonneuronal morphology in striatum after preconditioning ischemia. bcl-2 antisense oligodeoxynucleotides (ODNs), bcl-2 sense ODNs, or artificial cerebrospinal fluid (CSF, vehicle) was infused into the lateral ventricle for the 72 hours between the 20-minute ischemic preconditioning and the 60-minute period of ischemia. Antisense ODN treatment reduced expression of bcl-2 in the striatum and blocked the induction of tolerance by preconditioning ischemia. Sense and CSF treatments had no effect on either bcl-2 expression or tolerance. In this model of induced tolerance to focal ischemia, bcl-2 appears to be a major determinant.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number3
StatePublished - 2001


  • Antisense oligodeoxynucleotides
  • Ischemic tolerance
  • Striatum


Dive into the research topics of 'bcl-2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain'. Together they form a unique fingerprint.

Cite this