The phosphodiesterase-4 inhibitor rolipram protects from ischemic stroke in mice by reducing blood-brain-barrier damage, inflammation and thrombosis

Peter Kraft, Tobias Schwarz, Eva Goeb, Nadine Heydenreich, Marc Brede, Sven G. Meuth, Christoph Kleinschnitz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Blood-brain-barrier (BBB) disruption, inflammation and thrombosis are important steps in the pathophysiology of acute ischemic stroke but are still inaccessible to therapeutic interventions. Rolipram specifically inhibits the enzyme phosphodiesterase (PDE) 4 thereby preventing the inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to relief inflammation and BBB damage in a variety of neurological disorders. We investigated the therapeutic potential of rolipram in a model of brain ischemia/reperfusion injury in mice. Treatment with 10mg/kg rolipram, but not 2 mg/kg rolipram, 2 h after 60 min of transient middle cerebral artery occlusion (tMCAO) reduced infarct volumes by 50% and significantly improved clinical scores on day 1 compared with vehicle-treated controls. Rolipram maintained BBB function upon stroke as indicated by preserved expression of the tight junction proteins occludin and claudin-5. Accordingly, the formation of vascular brain edema was strongly attenuated in mice receiving rolipram. Moreover, rolipram reduced the invasion of neutrophils as well as the expression of the proinflammatory cytokines IL-1? and TNF? but increased the levels of TGF?-1. Finally, rolipram exerted antithrombotic effects upon stroke and fewer neurons in the rolipram group underwent apoptosis. Rolipram is a multifaceted antiinflammatory and antithrombotic compound that protects from ischemic neurodegeneration in clinically meaningful settings.
Original languageEnglish
Pages (from-to)80-90
JournalExperimental Neurology
Publication statusPublished - Sept 2013


  • Blood-brain-barrier
  • Phosphodiesterase inhibitor
  • Rolipram
  • Inflammation
  • Middle cerebral artery occlusion
  • Edema
  • Apoptosis
  • Thrombosis
  • Cytokines
  • Stroke

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