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Ameliorating mitochondrial dysfunction as a treatment of perinatal brain damage
Akerke Bissenbay, BSc; Anton Kichev, PhD.
Perinatal Brain Injury Group, King’s College London
Abstract
Brain injuries occurring during perinatal period are caused mainly by hypoxic-ischemic (HI)
events and/or inflammation and make up 70% in the overall child mortality and disabilities. HI
induced injury develops through complex cascade of pathophysiological processes with the
activation of both necrotic and apoptotic cell death leading to damage and death of neurons and
glial cells. During that processes mitochondrial dysfunction plays a primary role. Despite the
advances in the neonatal care in the last years the treatment of perinatal HI injury is still limited.
There is thus, an obvious need for more effective treatment strategies and mitochondria-
targeted treatments are promising candidates for research. Increasing body of evidence is
accumulating about the beneficial role of Methylene Blue (MB) treatment for improving the
mitochondrial function and cell survival in HI conditions. Our in vitro cell culture studies
confirmed for the first time the potential protective effect of MB on neuronal progenitor and
oligodendrocyte cell lines. The protective effect of MB was mediated through the inhibition of
reactive oxygen species (ROS) production by MB in both cell lines and restoration of hampered
ATP levels in oligodendrocyte precursor cell line during HI. In vitro studies with microglial cell
lines did not identified MB inhibitory role for microglial cells activation under inflammatory
conditions as previously suggested. In vivo studies with animal model of neonatal HI treated
with MB did not give conclusive results due to time limitations of this project. Despite the
promising results obtained with cell culture studies, there are still many unanswered questions
regarding the exact mechanism of MB action and its effect on HI induced perinatal brain injury.
Further studies are needed in order to determine the potential beneficial role of MB treatment in
the context of different perinatal brain injuries and main mechanisms by which MB protects
neuronal/glial cells.

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Abstract. Bissenbay Akerke

  • 1. Ameliorating mitochondrial dysfunction as a treatment of perinatal brain damage Akerke Bissenbay, BSc; Anton Kichev, PhD. Perinatal Brain Injury Group, King’s College London Abstract Brain injuries occurring during perinatal period are caused mainly by hypoxic-ischemic (HI) events and/or inflammation and make up 70% in the overall child mortality and disabilities. HI induced injury develops through complex cascade of pathophysiological processes with the activation of both necrotic and apoptotic cell death leading to damage and death of neurons and glial cells. During that processes mitochondrial dysfunction plays a primary role. Despite the advances in the neonatal care in the last years the treatment of perinatal HI injury is still limited. There is thus, an obvious need for more effective treatment strategies and mitochondria- targeted treatments are promising candidates for research. Increasing body of evidence is accumulating about the beneficial role of Methylene Blue (MB) treatment for improving the mitochondrial function and cell survival in HI conditions. Our in vitro cell culture studies confirmed for the first time the potential protective effect of MB on neuronal progenitor and oligodendrocyte cell lines. The protective effect of MB was mediated through the inhibition of reactive oxygen species (ROS) production by MB in both cell lines and restoration of hampered ATP levels in oligodendrocyte precursor cell line during HI. In vitro studies with microglial cell lines did not identified MB inhibitory role for microglial cells activation under inflammatory conditions as previously suggested. In vivo studies with animal model of neonatal HI treated with MB did not give conclusive results due to time limitations of this project. Despite the promising results obtained with cell culture studies, there are still many unanswered questions regarding the exact mechanism of MB action and its effect on HI induced perinatal brain injury. Further studies are needed in order to determine the potential beneficial role of MB treatment in the context of different perinatal brain injuries and main mechanisms by which MB protects neuronal/glial cells.