Your doctor will need to read this all. It talks about ebselen, Normobaric oxygen, lubeluzole, nitric oxide, Mitoquinone. I sure your doctor can rattle off all the research with these compounds and why none of it can be used for your recovery. There are only 211 supporting research articles for this writeup.
http://www.mdpi.com/2076-3921/3/3/472/htm
Rachel Shirley †,
Emily N. J. Ord †
and
Lorraine M. Work *
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed; E-Mail:
Lorraine.Work@glasgow.ac.uk; Tel.: +44-141-330-5869; Fax: +44-141-330-5339.
Received: 24 February 2014; in revised form: 8 May 2014 / Accepted: 14 May 2014 /
Published: 3 July 2014
Abstract
:
Transient or permanent interruption of cerebral blood flow by
occlusion of a cerebral artery gives rise to an ischaemic stroke leading
to irreversible damage or dysfunction to the cells within the affected
tissue along with permanent or reversible neurological deficit.
Extensive research has identified excitotoxicity, oxidative stress,
inflammation and cell death as key contributory pathways underlying
lesion progression. The cornerstone of treatment for acute ischaemic
stroke remains reperfusion therapy with recombinant tissue plasminogen
activator (rt-PA). The downstream sequelae of events resulting from
spontaneous or pharmacological reperfusion lead to an imbalance in the
production of harmful reactive oxygen species (ROS) over endogenous
anti-oxidant protection strategies. As such, anti-oxidant therapy has
long been investigated as a means to reduce the extent of injury
resulting from ischaemic stroke with varying degrees of success. Here we
discuss the production and source of these ROS and the various
strategies employed to modulate levels. These strategies broadly attempt
to inhibit ROS production or increase scavenging or degradation of ROS.
While early clinical studies have failed to translate success from
bench to bedside, the combination of anti-oxidants with existing
thrombolytics or novel neuroprotectants may represent an avenue worthy
of clinical investigation. Clearly, there is a pressing need to identify
new therapeutic alternatives for the vast majority of patients who are
not eligible to receive rt-PA for this debilitating and devastating
disease.
Keywords:
anti-oxidant; stroke; oxidative stress
1. Introduction
In addition to being the second leading cause of death worldwide [1], stroke is also the leading cause of acquired adult disability [2].
Stroke therefore has a very large socioeconomic impact with one third
of all stroke patients requiring permanent residential care, costing the
NHS in the UK £3.8 billion per annum [3].
The only approved pharmacological intervention for stroke is
intravenous administration of the thrombolytic, recombinant tissue
plasminogen activator (rtPA), within 4.5 h of the onset of ischaemia [4].
This short therapeutic window results in only 2%–5% of all stroke
patients receiving this intervention with successful reperfusion of the
brain occurring in only 50% of that cohort [5],
as such this is a disease with largely unmet clinical needs. Ischaemic
stroke (as opposed to haemorrhagic stroke) results from an
atherothrombotic or embolic blockage to a cerebral artery and accounts
for ~80% of all stroke cases. Finding a new pharmacological treatment
for stroke is incredibly complex for a number of reasons. The brain is a
highly metabolically active organ that relies on constant oxygen and
glucose supply from the circulation. The brain accounts for 2% of the
total body but requires 20% O2 and 2% of the entire body’s glucose consumption, although it performs no mechanical work or external secretory activity [6].
Storage of energy and metabolites within the brain is extremely low and
as such the brain is exceptionally sensitive to interruptions in blood
flow [7].
Although the brain is protected from systemic toxins under normal
physiological conditions by the blood-brain barrier (BBB), this is
broken down during cerebral ischaemia allowing infiltration of
inflammatory mediators and other potentially toxic molecules. Following
the onset of ischaemia numerous pathways contribute to brain injury,
there is extensive crosstalk between these deleterious pathways with
them also, in the main, existing as positive feedback loops serving to
amplify insult. In what is the most significant challenge of stroke
treatment, the majority of damage occurs within minutes and the acute
hours following cerebral ischaemia and as such, stroke treatment at
present remains mainly preventative. Here, we will discuss the source
and consequence of reactive oxygen species (ROS) imbalance following
cerebral ischaemia/reperfusion before considering anti-oxidant
strategies attempted clinically based on the pre-clinical evidence for
each. What is clear is that while the contributory role of ROS in stroke
cannot be disputed, the relative merit of anti-oxidant therapy alone
has yet to be established and combined therapy may be where agents
modulating the balance of ROS prove beneficial.
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