Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 33,860 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label Neutrophil extracellular traps. Show all posts
Showing posts with label Neutrophil extracellular traps. Show all posts
Didn't your doctor and hospital start working on a solution for this 5 years ago? NO? So, the BOARD OF DIRECTORS IS COMPLETELY INCOMPETENT IN RUNNING A STROKE HOSPITAL!
1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
2Department of Neurology, Jiangbing Hospital, Nanning, China
3Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
Ischemic stroke remains a leading cause of mortality and disability, with many patients failing to benefit from reperfusion therapies due to lysis-resistant thrombus formation and severe neuroinflammation. This highlights an urgent need to target the fundamental mechanisms linking these two processes. Neutrophil extracellular traps (NETs)—web-like structures of DNA and cytotoxic proteins—have emerged as a critical mediator of stroke pathology. While essential for host defense, their dysregulated formation in the cerebral microvasculature drives a vicious cycle of tissue injury. This review synthesizes evidence demonstrating that NETs are not mere bystanders but active drivers of stroke pathology. We dissect the core mechanisms by which they mediate three primary detrimental effects: (1) promoting stable, lysis-resistant thrombi, which directly contributes to poor clinical outcomes; (2) compromising blood–brain barrier integrity; and (3) amplifying the neuroinflammatory cascade. Furthermore, we evaluate the clinical utility of NETs as powerful biomarkers for diagnosis and prognosis, and we critically analyze emerging therapeutic strategies aimed at dismantling them. While targeting NETs with agents like DNase I or PAD4 inhibitors holds immense promise, we argue that significant translational challenges—such as ensuring therapeutic specificity and defining the optimal treatment window—must be overcome. In conclusion, targeting the thrombo-inflammatory functions of NETs represents a paradigm shift from a purely fibrin-centric view of stroke, opening new avenues for developing more effective therapies.
Described a problem, suggested further research, did not specify WHOM was going to accomplish that! Useless! I expect stroke researchers to solve problems; not just tell us they exist. With proper leadership stroke could easily be solved.
Subarachnoid hemorrhage (SAH) is a clinical condition with a high
mortality rate that causes in survivors’ permanent disabilities. Among
complications after SAH, the most important is the delayed large vessel
vasospasm, which have been intensively studied. It is usually seen after
day 3 of hemorrhage, and it could contribute to another complication
that is delayed cerebral ischemia (DCI). In contrast, arteriolar
vasospasm, known as microvasospasm, has been reported to occur in the
subacute phase, and it is believed to contribute to DCI. Delayed
vasospasm is usually treated with endothelin receptor antagonist drugs
(e.g., clazosentan sodium), which, however, cannot completely prevent
DCI. Few studies focused on the mechanism of microvasospasms, and no
studies have revealed pathological mechanisms underlying subacute
microvasospasms.
The aim of the study is to elucidate the mechanism of microvasospasm
through an animal model with intravital 2-photon microscopy,
investigating effects of neutrophil removal and, in particular, of
Neutrophil Extracellular Traps (NETs) released by neutrophils. NETs are
DNA histone complexes released by activated neutrophils, composed of DNA
and various antibacterial proteins that have the original purpose of
capturing and neutralizing pathogens. Despite that, NET can have a
disadvantage of damaging host cells, and, in particular, they are known
to play a crucial role in brain damage after SAH.
The author first established an SAH mouse model with a cranial window of 3 x 3 mm, as previously described.1,2
Briefly, they injected 40 uL of blood from the hearts of littermate
mice, in the prechiasmatic cistern using a syringe coated with a minimal
amount of heparin. Erythrocytes were previously labeled with
phycoerythrin (PE) or fluorescein isothiocyanate (FITC) to visualize
their distribution, and neutrophils were labeled with a PE-conjugated
anti Ly6G antibody. All was visualized and recorded by time-lapse
imaging through 2-photon microscopy. Of course, sham animals underwent
the same procedure except for blood injection. The authors observed that
both cells population were distributed to the perivascular space of the
pial arterioles. Erythrocytes disappeared gradually and almost
completely after 2 to 5 days. Concurrently, the pial arterioles were
constricted and appeared as microvasospam, as illustrated in Figure 1F.
Figure 1E-F.
The source of infiltrating neutrophils was checked through the use of
LysM EGFP reporter mice in which neutrophils robustly express a green
fluorescent protein: The authors verified that the source of neutrophil
infiltration was the circulation of the host but not the injected blood.
The authors then depleted neutrophils from the host mice by
intraperitoneal administration of neutrophil-specific antibody (200 ug
of rat anti-Ly6G antibody) 1 day and 1 hour before SAH, and then
evaluated microvasospasms, visualized as pearl-string-like stenosis:
Microvasospasms were significantly reduced in the neutrophil depleted
group. For the control group, an equal amount of the isotype control was
injected. Nakagawa and colleagues observed that in the control group,
the number of infiltrating neutrophils was correlated with the volume of
accumulated erythrocytes, speculating that neutrophil infiltration in
the perivascular space may have been triggered by erythrocyte
accumulation.
Focusing on NETs formation, to confirm their presence in the
perivascular space, a marker for NETs (SYTOX Green) was intracisternally
injected, indicating that, after SAH, NETs are released in the
perivascular space. To test if NETs cause microvasospasm, the authors
administered DNase, a NETs inhibitor, at 1 day after SAH in order to
remove them in perivascular space. As expected, microvasospasms were
significantly suppressed after DNase treatment, and blood flow velocity
at day 5 significantly improved.
In conclusion, the author established an experimental system to
investigate events occurring after SAH, demonstrating accumulation of
erythrocytes in the perivascular space, the subsequent infiltration of
neutrophils, and, for the first time, the presence of a large amount of
NETs, leading to the development of microvasospasm. NETs were, in fact,
attached to the arterioles, suggesting that they may directly damage the
endothelium or vascular smooth muscle of the arterioles.
Some limitations of the study are due to the limited cranial window
to observe a relatively small part of the cerebral cortex, so results
may not be generalizable to the entire brain. Furthermore, there is a
need for additional research to verify the precise nature of
perivascular NETS and their pathological effects.
Thrombosis
is linked to neutrophil release of neutrophil extracellular traps
(NETs). NETs are proposed as a mechanism of resistance to thrombolysis.
This study intends to analyze the composition of thrombi retrieved after
mechanical thrombectomy, estimate the age and organization of thrombi,
and evaluate associations with the use of thrombolysis, antiplatelets,
and heparin.
METHODS:
This
retrospective observational study involved 72 samples (44 from cerebral
and 28 coronary arteries), which were stained with hematoxylin and
eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B
(histone H2B) antibody, representing different components in NET
formation, all detectable during the later stages of NETosis, for
histochemical and digital quantification of NET content. The
histological and morphological evaluations of the specimens were
correlated, through univariate and mediation analyses, with clinical
information and therapy administered before intervention.
RESULTS:
The
results demonstrated that the composition of cerebral and coronary
thrombi differs, and there were significantly more lytic cerebral
thrombi than coronary thrombi (66% versus 14%; P=0.005). There
was a considerably higher expression of NETs in the cerebral thrombi as
testified by the higher expression of H2B (P=0.031). Thrombolysis
was remarkably associated with higher NE positivity (average marginal
effect, 6.461 [95% CI, 0.7901–12.13]; P=0.02555), regardless of
the origin of thrombi. There was no notable association between the
administration of antiaggregant therapy/heparin and H2B/NE amount when
adjusted for the thrombus location. Importantly, the age of the thrombus
was the only independent predictor of NET content without any mediation
of the thrombolytic treatment (P=0.014).
CONCLUSIONS:
The
age of the thrombus is the driving force for NET content, which
correlates with impaired clinical outcomes. The therapy that is
currently administered does not modify NET content. This study supports
the need to investigate new pharmacological approaches added to
thrombolysis to prevent NET formation or enhance their disruption, such
as recombinant human DNase I (deoxyribonuclease I).
DId your doctor and stroke hospital get research going on therapeutic targets in patients with acute stroke? It has only been 3 years. If nothing was done, WHY THE HELL HAVEN'T YOU FIRED THE BOARD OF DIRECTORS? They are the responsible party setting the goals of the stroke hospital. If their goal is not 100% recovery, they don't belong there.
› Author AffiliationsFinancial support:
This work was supported in part by grants from the Spanish Fondo de
Investigaciones Sanitarias Carlos III [FIS13/00016] Fondos FEDER, una
forma de hacer Europa, Fundación Española de Trombosis y Hemostasia,
Sociedad Valenciana de Cardiología, Consellería Valenciana d’Educació
(ACIF/2016/465), GV and RETICS networks INVICTUS (RD12/0014/0004) and
INVICTUS+ (RD16/0019/0008) ‘Instituto de Salud Carlos III’.
Neutrophil extracellular traps (NETs) are networks of DNA, histones,
and proteolytic enzymes produced by activated neutrophils through
different mechanisms. NET formation is promoted by activated platelets
and can in turn activate platelets, thus favoring thrombotic processes.
NETs have been detected in venous and arterial thrombosis, but data in
stroke are scarce. The aim of this study was to evaluate NETs in the
plasma of patients with acute ischemic stroke and their potential
association with baseline clinical characteristics, stroke severity, and
one-year clinical outcomes. The study included 243 patients with acute
ischemic stroke. Clinical and demographic data and scores of stroke
severity (NIHSS and mRs) at onset and discharge were recorded. Markers
of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3
(citH3)), were determined in plasma. Patients were followed-up for 12
months after the ischemic event. NETs were significantly elevated in the
plasma of patients with acute ischemic stroke when compared to healthy
subjects. NETs were increased in patients who were over 65 years of age
and in those with a history of atrial fibrillation (AF), cardioembolic
stroke, high glucose levels, and severe stroke scores at admission and
discharge. In multivariate analysis, elevated levels of citH3, the most
specific marker of NETs, at onset were independently associated with AF
and all-cause mortality at oneyear follow-up. NETs play a role in the
pathophysiology of stroke and are associated with severity and
mortality. In conclusion, citH3 may constitute a useful prognostic
marker and therapeutic target in patients with acute stroke.
Wenbo He
Zuoli Wu
Ying Liu
Ziming Ye
