Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia

Yukiko Kasahara, Akihiko Taguchi, Hisakazu Uno, Akiko Nakano, Takayuki Nakagomi, Haruka Hirose, David Stern, Tomohiro Matsuyama

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The beneficial effects of angiotensin II type 1 (AT1) receptor blockers (ARB) in cerebrovascular disease have been shown in clinical trials. However, the effects of ARBs vary based on their unique pharmacologic properties. In this study, we focused on telmisartan, a fat-soluble ARB with selective peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity, and investigated its effects on ischemic injury in cerebral vasculature using murine models of both transient and permanent focal ischemia. Analysis by triphenyltetrazolium-staining revealed that pre-treatment of mice with telmisartan reduced stroke volume 72 h after the transient ischemic insult in a dose-dependent manner, though such treatment did not reduce stroke volume due to permanent ischemia. Transient ischemia induced pro-inflammatory adhesion molecules, such as ICAM-1 and P-selectin in the ischemic region, and treatment with telmisartan diminished the expression of these adhesion molecules with diminished infiltration of inflammatory cells. The beneficial effect of telmisartan was attenuated, in part, by administration of a PPARγ antagonist. Treatment with valsartan (an ARB without PPARγ agonist activity) also decreased ischemic injury after transient ischemia, though to a lesser extent than telmisartan. Our findings indicate that telmisartan has a beneficial effect in a murine model of ischemia/reperfusion injury through blockade of AT1 receptors, and, in addition, due to a positive effect via its specific anti-inflammatory PPARγ agonist activity.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalBrain Research
Volume1340
DOIs
StatePublished - Jun 22 2010
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Ischemia
Wounds and Injuries
Valsartan
Stroke Volume
Angiotensin II Type 1 Receptor Blockers
Cerebrovascular Disorders
Angiotensin Type 1 Receptor
P-Selectin
Intercellular Adhesion Molecule-1
Reperfusion Injury
telmisartan
Anti-Inflammatory Agents
Fats
Clinical Trials
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Kasahara, Y., Taguchi, A., Uno, H., Nakano, A., Nakagomi, T., Hirose, H., ... Matsuyama, T. (2010). Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. Brain Research, 1340, 70-80. https://doi.org/10.1016/j.brainres.2010.03.101

Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. / Kasahara, Yukiko; Taguchi, Akihiko; Uno, Hisakazu; Nakano, Akiko; Nakagomi, Takayuki; Hirose, Haruka; Stern, David; Matsuyama, Tomohiro.

In: Brain Research, Vol. 1340, 22.06.2010, p. 70-80.

Research output: Contribution to journalArticle

Kasahara, Y, Taguchi, A, Uno, H, Nakano, A, Nakagomi, T, Hirose, H, Stern, D & Matsuyama, T 2010, 'Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia', Brain Research, vol. 1340, pp. 70-80. https://doi.org/10.1016/j.brainres.2010.03.101
Kasahara Y, Taguchi A, Uno H, Nakano A, Nakagomi T, Hirose H et al. Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. Brain Research. 2010 Jun 22;1340:70-80. https://doi.org/10.1016/j.brainres.2010.03.101
Kasahara, Yukiko ; Taguchi, Akihiko ; Uno, Hisakazu ; Nakano, Akiko ; Nakagomi, Takayuki ; Hirose, Haruka ; Stern, David ; Matsuyama, Tomohiro. / Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia. In: Brain Research. 2010 ; Vol. 1340. pp. 70-80.
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