Ischemic stroke brain sends indirect cell death signals to the heart

Hiroto Ishikawa, Naoki Tajiri, Julie Vasconcellos, Yuji Kaneko, Osamu Mimura, Mari Dezawa, Cesar V. Borlongan

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


Background and Purpose: Ischemic stroke is a leading cause of mortality and morbidity in the world and may be associated with cardiac myocyte vulnerability. However, it remains uncertain how an ischemic brain contributes to cardiac alternations. Here, we used experimental stroke models to reveal the pathological effects of the ischemic brain on the heart. Methods: For the in vitro study, primary rat neuronal cells were subjected to 90-minute oxygen-glucose deprivation (OGD). Two hours after OGD, the supernatant was collected and cryopreserved until further biological assays. Primary rat cardiac myocytes were exposed to ischemic-reperfusion injury and subsequently to the supernatant derived from either the OGD or non-OGD-exposed primary rat neuronal cells for 2, 6, 24, or 48 hours. Thereafter, we measured cell viability and mitochondrial activity in rat cardiac myocytes. For the in vivo study, we subjected adult rats to transient middle cerebral artery occlusion, and their brains and hearts were harvested for immunohistochemical analyses at 3 months later. Results: The supernatant from the OGD, but not the non-OGD-exposed primary rat neuronal cells, caused significant reduction in cell viability and mitochondrial activity in rat cardiac myocytes. Ischemic stroke animals displayed phenotypic expression of necrosis, apoptosis, and autophagy in their hearts, which paralleled the detection of these same cell death markers in their brains. Conclusions: Ischemic stroke was accompanied by cardiac myocyte death, indicating a close pathological link between brain and heart. These results suggest a vigilant assessment of the heart condition in stroke patients, likely requiring the need to treat systemic cardiac symptoms after an ischemic brain episode.

Original languageEnglish
Pages (from-to)3175-3182
Number of pages8
Issue number11
Publication statusPublished - 2013 Nov


  • Apoptosis
  • Autophagy
  • Brain ischemia
  • Cardiac
  • Myocytes
  • Necrosis


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