SCAN: New strategies to prevent brain damage due to hypoxia-ischemia and reperfusion

Scan Seminar

Title: Preconditioning triggered by carbon monoxide: new strategies to prevent brain damage due to hypoxia-ischemia and reperfusion - in vitro and in vivo approach

Speaker: Helena Vieira

From: Animal Cell Technology Laboratory

Abstract:

Preconditioning triggered by carbon monoxide: new strategies to prevent brain
damage due to hypoxia-ischemia and reperfusion - in vitro and in vivo approach
The main intracellular sources of reactive oxygen species (ROS) encompass the
mitochondrial respiratory chain complexes (1-3% of the oxygen reacting with the
respiratory chain is incompletely reduced to the superoxide anion and hence to
hydrogen peroxide) and a number of oxidases (among which the plasma membrane
NADPH oxidase is one of the major players). It has been more and more recognized
that intracellular ROS generation plays a role as messengers in the activation of several
specific signalling pathways. Herein, carbon monoxide is explored as an inducer of
ROS generation. Carbon monoxide (CO) is shown to (i) induce preconditioning (PC)
phenomenon, (ii) to activate endogenous cellular mechanisms of cytoprotection and (iii)
to prevent apoptosis; in primary cultures of neurons and astrocytes. The role of
mitochondria in the modulation of PC and apoptosis is highlighted, as well as ROS
signalisation via changes in glutathione levels and key protein glutathionylation. Among
the in vitro approaches, a hypoxia/ischemia and reperfusion (HIR) model of astrocytes
grown in bioreactors (a fully controlled environment) has also demonstrated the ability
of CO as anti-apoptotic molecule. In vivo studies about the ROS signalling in CO
neuroprotection are under development using a perinatal model of cerebral HIR
(Vannucci model), revealing promising results.