http://stroke.ahajournals.org/content/44/11/3175.abstract.html?etoc
- Hiroto Ishikawa, MD, PhD;
- Naoki Tajiri, PT, PhD;
- Julie Vasconcellos, BS;
- Yuji Kaneko, PhD;
- Osamu Mimura, MD, PhD;
- Mari Dezawa, MD, PhD;
- Cesar V. Borlongan, PhD
+ Author Affiliations
- Correspondence to Cesar V. Borlongan, PhD, Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd MDC78, Tampa, FL 33612. E-mail cborlong@health.usf.edu
Abstract
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.
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