As a thrombosis or emboli cause a decrease in blood supply to the brain tissue, events occur at the cellular level, referred to as the ischemic cascade
. Neurons and support cells require a careful balance of variables such as temperature, pH, nutrition, and waste removal in their environment to function optimally (Hinkle & Bowman, 2003).
A lack of blood supply to the ischemic area of the brain known as the penumbra initiates an ischemic cascade
whereby brain function stops if oxygen deprivation exceeds 60 to 90 seconds and brain tissue dies within 3 hours of anoxia leading to cerebral infarction.
Decreased blood flow to the brain deprives the brain of oxygen, triggering the ischemic cascade
that includes calcium influx, overstimulation of excitatory amino acids, and overproduction of free radicals.
We believe the model of postmortem CSF may partly reproduce mechanisms underlying the ischemic cascade
of events leading to stroke lesions and, as such, may confer scientific plausibility to the biomarkers identified.
Fig 1 provides an overview of these alterations, referred to as the ischemic cascade
. Improved understanding of this pathophysiology has led basic science researchers to investigate new treatments for ischemic injury.
The exact level at which lubeluzole acts in the ischemic cascade
remains to be determined.
This ischemic cascade
continues as pronounced cellular and neurological dysfunction ensue and excitatory neurotransmitters, such as glutamate and aspartate are released into the extracellular space.
The ischemic cascade
is a complex process that occurs at the cellular level.
Ischemic stroke is considered to be caused by decreased blood flow to brain tissue, followed by the activation of the ischemic cascade
which leads to cell death and severe neuronal damage , which includes apoptosis, oxidative stress, inflammation, and calcium overload.
Myocardial ischemia involves a typical sequence of events termed the "ischemic cascade
," shown in Figure 2.
The lack of oxygen results in energy deprivation and the ischemic cascade
starts with an arterial thromboembolic episode.
Inflammation is a crucial contributor in the ischemic cascade
after cerebral ischemia that results in harmfully augmenting "secondary injury".