Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia

On page 14 of the PDF you'll notice some post stroke treatment options. Bring them to your doctor's attention.  You'll want  this planned out before your next stroke because you may not be lucid in the ER. And telling them to look this up in Deans' Stroke Musings will not go over well.

 Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia

 Joanna M Wiero ´nska 1, 

Paulina Cie´slik 1 

and Leszek Kalinowski 2,3,4,*





Citation: Wiero ´nska, J.M.; Cie´slik, P.;
Kalinowski, L. Nitric OxideDependent Pathways as Critical
Factors in the Consequences and
Recovery after Brain Ischemic
Hypoxia. Biomolecules 2021, 11, 1097.
https://doi.org/10.3390/biom11081097
Academic Editor: Jerzy Beltowski
Received: 31 May 2021
Accepted: 20 July 2021
Published: 26 July 2021
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1 Maj Institute of Pharmacology, Polish Academy of Sciences, Sm ˛etna Street 12, 31-343 Kraków, Poland;
wierons@if-pan.krakow.pl (J.M.W.); cieslik@if-pan.krakow.pl (P.C.)
2 Department of Medical Laboratory Diagnostics—Biobank Fahrenheit BBMRI.pl,
Medical University of Gdansk, Debinki Street 7, 80-211 Gdansk, Poland
3 Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7,
80-211 Gdansk, Poland
4 BioTechMed Center/Department of Mechanics of Materials and Structures, Gdansk University of Technology,
Narutowicza 11/12, 80-223 Gdansk, Poland
* Correspondence: leszek.kalinowski@gumed.edu.pl; Tel.: +48-58-349-1182

Abstract: 

Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric
oxide (NO•), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal
and glial activity constitutes the crucial factor that contributes to the development of pathological
changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood
flow is the massive production of reactive oxygen and nitrogen species (ROS/RNS) in neurons due
to NO•synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic
neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to
place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory
proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress
that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the
late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1α (HIF-1α) and HIF-1α-dependent
genes activated in reactive astrocytes play essential roles in this process. The review summarizes the
roles of NO•-dependent pathways in the early and late aftermath of stroke and treatments based on
the stimulation or inhibition of particular NO•synthases and the stabilization of HIF-1α activity.