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

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

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

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
Volume21
Issue number3
DOIs
StatePublished - 1 Jan 2001

Fingerprint

Ischemia
Brain
Ischemic Preconditioning
Oligodeoxyribonucleotides
Putamen
Infarction
Therapeutics
Lateral Ventricles
Middle Cerebral Artery
Cerebrospinal Fluid
Western Blotting

Keywords

  • Antisense oligodeoxynucleotides
  • Ischemic tolerance
  • Striatum

Cite this

Shimizu, Shigetoshi ; Nagayama, Tetsuya ; Jin, Kunlin ; Zhu, Li ; Loeffert, J. Eric ; Watkins, Simon C. ; Graham, Steven H. ; Simon, Roger P. / bcl-2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain. In: Journal of Cerebral Blood Flow and Metabolism. 2001 ; Vol. 21, No. 3. pp. 233-243.
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bcl-2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain. / Shimizu, Shigetoshi; Nagayama, Tetsuya; Jin, Kunlin; Zhu, Li; Loeffert, J. Eric; Watkins, Simon C.; Graham, Steven H.; Simon, Roger P.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 21, No. 3, 01.01.2001, p. 233-243.

Research output: Contribution to journalArticle

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