7 lifestyle choices stroke experts avoid

 This is just a laundry list of possible points to use to blame the patient for their stroke. You'll have to scream at your incompetent? doctor for suggesting these bullshit excuses!

7 lifestyle choices stroke experts avoid

Stroke specialists emphasize avoiding prolonged sitting, smoking, excessive alcohol, and diets high in sodium or unhealthy fats to protect vascular health. They highlight the importance of regular exercise, blood pressure monitoring, and routine screenings to detect hidden risks early. Recognizing both common and subtle stroke symptoms ensures timely medical intervention and better outcomes.

References

4 habits that are quietly impacting your stroke risk | EatingWell
7 Things Stroke Doctors Say You Should Never, Ever Do | HuffPost
7 things stroke doctors say you should never, ever do | HuffPost
4 things cardiologists say to do to reduce your stroke risk | EatingWell
Healthy lifestyle behaviors can prevent up to 80% of strokes | Midland Reporter-Telegram
Risk Factors for Stroke | Stroke | CDC | cdc.gov
Stroke Prevention: 10 Ways to Lower Your Risk of a Stroke | healthline.com
Let’s Talk About Lifestyle Changes to Prevent Stroke | stroke.org
Preventing Stroke | Stroke | CDC | cdc.gov
7 everyday habits that quietly raise your stroke risk | Secret Life of Mom
Top 10 Foods to Avoid After a Stroke: Healthy Alternatives & Diet Tips | drvikasneuro.com
10 Foods to Avoid After Having a Stroke | Flint Rehab | flintrehab.com
You'd never guess this subtle sign of a stroke | HuffPost

Prolonged Sitting Harms Vascular Function

©Photo by Wolfgang Kumm/picture alliance via Getty Images. A woman sits on a chair and works on her laptop at the Bundeskanzleramt in Berlin, Germany, 22 September 2015. PHOTO: WOLFGANG KUMM/DPA | usage worldwide (Photo by Wolfgang Kumm/picture alliance via Getty Images)

Spending long periods sitting, whether at a desk, in a car, or in front of a screen, can impair blood vessel function, reduce circulation, and increase arterial stiffness. These changes contribute to a pro-inflammatory state that raises the risk of stroke, even in people who meet daily exercise recommendations. Breaking up sedentary time with regular movement can help protect vascular health.

Regular Exercise Helps Prevent Arterial Plaque Buildup

©Photo by Ulrich Baumgarten via Getty Images. GERMANY - FEBRUARY 21: Sunday walk in a Park in Bad Sassendorf (North Rhine-Westphalia). (Photo by Ulrich Baumgarten via Getty Images)

Engaging in approximately 30 minutes of moderate exercise five times a week can help keep blood vessels free from plaque. This reduces the risk of arterial blockages that may lead to stroke. Activities such as walking, cycling, gardening, or group workouts all contribute to maintaining healthy circulation.

Short Activity Breaks Protect Vascular Health

©Photo by Ute Grabowsky/Photothek via Getty Images. BONN, GERMANY - JULY 4: A man stretches his wrist at his desk during an active break in the office on July 4, 2024 in Bonn, Germany. (Photo by Ute Grabowsky/Photothek via Getty Images)

Breaking up long periods of sitting with short movement breaks every 45–60 minutes can help reduce the negative effects on vascular health. Light activities such as stretching, walking, or calf raises improve blood flow and reduce arterial stiffness. These simple actions support circulation and may lower the risk of stroke associated with prolonged sedentary behavior.

High Blood Pressure as the Leading Stroke Risk

©Photo by RICCARDO MILANI/Hans Lucas/AFP via Getty Images. Illustration of a woman using a blood pressure monitor (tensiometre) at home in Paris, France, on September 1, 2025. A woman uses an Omron blood pressure monitor to monitor her health by measuring her blood pressure (tension arterielle) every morning. (Photo by Riccardo Milani / Hans Lucas via AFP) (Photo by RICCARDO MILANI/Hans Lucas/AFP via Getty Images)

High blood pressure, or hypertension, is the most significant modifiable risk factor for stroke. Often called the "silent killer" because it typically has no symptoms, it can damage arteries over time and greatly increase stroke risk. Experts estimate that eliminating high blood pressure could prevent up to 60% of strokes, underscoring the importance of regular monitoring and treatment.

Target Blood Pressure for Stroke Prevention

©Photo by Hendrik Schmidt/picture alliance via Getty Images. 09 April 2026, Saxony, Chemnitz: A nurse measures the blood pressure of an elderly patient with a blood pressure monitor in the geriatric ward at Chemnitz DRK Hospital. The geriatric ward specializes in medical care for elderly patients. Photo: Hendrik Schmidt/dpa (Photo by Hendrik Schmidt/picture alliance via Getty Images)

Cardiologists advise maintaining blood pressure below 130/80 mm Hg to lower the risk of stroke and other cardiovascular events. This target can often be reached through lifestyle changes such as a low-sodium diet, regular exercise, and adherence to prescribed medications. Monitoring blood pressure at home helps track progress and guide treatment adjustments.

Home Blood Pressure Monitors Aid Hypertension Management

©Photo By BSIP/UIG Via Getty Images. Blood Pressure At 10,7 And Pulse At 66 Beats/Minute. (Photo By BSIP/UIG Via Getty Images)

Regularly checking blood pressure at home allows individuals to monitor their progress and see if lifestyle changes or medications are working effectively. Cardiologists recommend using a home monitor to help maintain target blood pressure levels, which is a key factor in reducing the risk of stroke and other cardiovascular events.

Routine Screenings Detect Hidden Stroke Risks

©Photo by Justin Sullivan/Getty Images. OAKLAND, CA - JULY 9: Nurse Melba Benedict (R) checks Negash Berhe's blood pressure July 9, 2003 at Highland Hospital in Oakland, California. In a report released July 9, researchers have found that high blood pressure is on the rise again in the United States, reversing a decade-long downward trend for the major cause of heart attacks and strokes. (Photo by Justin Sullivan/Getty Images)

Many stroke risk factors, such as high blood pressure, high cholesterol, and high blood sugar, develop without noticeable symptoms. Regular medical check-ups allow these conditions to be detected early through routine screenings. Early identification and treatment can significantly reduce the likelihood of stroke and improve long-term health outcomes.

Past Stroke Greatly Increases Future Stroke Risk

©Graphic by AFP via Getty Images. Graphic explaining the different kinds of strokes and their after effects. (Graphic by AFP via Getty Images)

People who have experienced a stroke or transient ischemic attack (TIA) face a higher risk of having another stroke. A family history of stroke can also elevate this risk. Regular medical monitoring and proactive management of other risk factors are important to help reduce the likelihood of recurrence.

Doctors Review Non-Modifiable Stroke Risk Factors

©Photo by Lauren Petracca/For The Washington Post via Getty Images. CHEEKTOWAGA, NY - MAY 5: Dr. Christopher Kerr and Dr. Megan O'Shea Farrell talk about a patient at Hospice Buffalo in Cheektowaga, NY on Tuesday, May 5, 2026. (Photo by Lauren Petracca/For The Washington Post via Getty Images)

During routine check-ups, doctors can evaluate stroke risk factors that cannot be changed, such as age, sex, race, and personal or family history. Understanding these factors helps healthcare providers tailor prevention strategies and recommend appropriate screenings. This proactive approach supports early detection and management of other modifiable risks.

Smoking Gradually Narrows Blood Vessels

©Photo by Jens Kalaene/picture alliance via Getty Images. 11 June 2026, Berlin: A woman is holding a smoking cigarette. Photo: Jens Kalaene/dpa (Photo by Jens Kalaene/picture alliance via Getty Images)

Smoking damages blood vessels, causing them to narrow over time. This narrowing can restrict blood flow and increase the likelihood of blockages, which may lead to a stroke. Avoiding tobacco use is an important step in reducing stroke risk.

Quitting Smoking Significantly Lowers Stroke Risk

©Photo credit should read CFOTO/Future Publishing via Getty Images. HANDAN, CHINA - MAY 30, 2022 - Volunteers use performance art to persuade citizens to quit smoking in Handan, Hebei Province, China, May 30, 2022. May 31 is World No Tobacco Day. (Photo credit should read CFOTO/Future Publishing via Getty Images)

Cigarette smoking is a major risk factor for stroke, as it damages blood vessels and increases clot formation. Quitting smoking can substantially reduce this risk and improve overall cardiovascular health. Health experts recommend combining medical support, behavioral strategies, and social encouragement to successfully stop smoking and protect brain health.

Avoiding Secondhand Smoke Reduces Stroke Risk

©photo by Mike Kemp/In Pictures via Getty Images. Two men exhale clouds of cigarette smoke on the street in the City of London on 7th February 2023 in London, United Kingdom. Despite fewer people smoking, it remains the leading cause of preventable death and disease in the UK. (photo by Mike Kemp/In Pictures via Getty Images)

Secondhand smoke can damage blood vessels and contribute to the development of stroke. Avoiding environments where tobacco is smoked helps lower this risk and supports overall cardiovascular health. This preventive measure is part of broader lifestyle changes that reduce the likelihood of stroke.

Excessive Alcohol Intake Raises Blood Pressure

©Photo by: Universal Archive/Universal Images Group via Getty Images. Blood Pressure Measurement. (Photo by: Universal Archive/Universal Images Group via Getty Images)

Drinking alcohol in amounts above recommended limits can increase blood pressure, which is a major modifiable risk factor for stroke. Health guidelines suggest that women should limit alcohol to no more than one drink per day and men to no more than two. Consistently exceeding these limits may contribute to long-term cardiovascular harm.

Alcohol Before Bed Disrupts Sleep and Blood Pressure

©Photo by Thomas Eisenhuth/picture alliance via Getty Images. ILLUSTRATION - A man drinks from a bottle of wine in Dresden (Saxony), Germany, 21 May 2015. Photo: Thomas Eisenhuth/dpa -NO WIRE SERVICE- | usage worldwide (Photo by Thomas Eisenhuth/picture alliance via Getty Images)

Consuming alcohol in the hours before bedtime can interfere with normal sleep cycles, particularly by suppressing REM sleep early in the night and causing fragmented rest later. This disruption prevents the typical nighttime drop in blood pressure, placing extra strain on the cardiovascular system. Over time, such effects can contribute to elevated stroke and heart disease risk.

Alcohol Moderation and Timing Reduce Stroke Risk

©Photo by Fairfax Media via Getty Images via Getty Images. (AUSTRALIA OUT) Red wine poored into a glass (Photo by Fairfax Media via Getty Images via Getty Images)

Limiting alcohol consumption is a key factor in lowering stroke risk, alongside healthy eating and regular exercise. Research shows that drinking before bedtime can disrupt sleep patterns and prevent the normal nighttime drop in blood pressure, increasing cardiovascular strain. Experts recommend avoiding alcohol in the hours before sleep to support heart health and reduce stroke risk.

High Sodium Intake Increases Stroke Risk

©Photo by Tom Kelley/Getty Images. Close-up view of a glass salt shaker on its side and spilled salt on a white, reflective surface, April 8, 2011. (Photo by Tom Kelley/Getty Images)

Consuming too much sodium can raise blood pressure, which damages blood vessels and heightens the risk of stroke. Limiting salt in the diet helps protect cardiovascular health and reduces strain on the heart. This preventive measure is important for lowering the likelihood of both initial and recurrent strokes.

Saturated and Trans Fats Promote Artery Plaque Formation

©Photo by ROBERT SULLIVAN/AFP via Getty Images. Doughnuts from Dunkin" Donuts, French fries from McDonald's and fried chicken from Kentucky Fried Chicken are displayed 27 September 2006 in Miami, Florida. Three years after New York City banned smoking in restaurants, health officials are talking about prohibiting something they say is almost as bad, artificial trans fatty acids. The New York City health department announced a proposal 27 September that would bar cooking at any of the city's 24,600 food service establishments using ingredients that contain the artery-clogging substance, commonly listed on food labels as partially hydrogenated oil which would create a huge problem for national fast food chains. Artificial trans fats are found in some shortenings, margarine and frying oils and turn up in foods from pie crusts to French fries to doughnuts. AFP PHOTO/ROBERT SULLIVAN (Photo by ROBERT SULLIVAN / AFP) (Photo by ROBERT SULLIVAN/AFP via Getty Images)

Consuming large amounts of saturated and trans fats can lead to the buildup of plaque in the arteries. This buildup narrows the arteries, restricting blood flow and increasing the risk of stroke. Avoiding foods high in these fats, such as fried fast food and cream-based sauces, can help protect cardiovascular health.

Plant-Rich Diets Linked to Lower Stroke Risk

©Photo by: Costanza Sigismondi/REDA/Universal Images Group via Getty Images. A series of mediterrean tomatoes receipe with watermelon, black olives and cucumber, with origano, served in colored ceramic plate; vinylic background, space to write, soft blue cotton fabric on the table,. (Photo by: Costanza Sigismondi/REDA/Universal Images Group via Getty Images)

Diets centered on fruits, vegetables, whole grains, and lean proteins support cardiovascular health and help reduce the risk of stroke. Research highlights that limiting saturated fats, salt, and added sugars while emphasizing plant-based foods can improve blood pressure and blood vessel health. Such eating patterns, including Mediterranean-style diets, are associated with a lower likelihood of stroke and related complications.

Subtle Symptoms May Signal Certain Types of Stroke

©Photo by: BSIP/Universal Images Group via Getty Images. Illustration of a cerebrovascular accident (CVA) caused by ischemia. Ischemic accidents are due to the occlusion of a cerebral artery, or one leading to the brain (internal or vertebral carotids). The brain is therefore partially deprived of oxygen and glucose. This occlusion leads to a cerebral infarction. This occlusion is mainly caused by an obstructive atheroma or a clot (formed locally or by embolism). (Photo by: BSIP/Universal Images Group via Getty Images)

Some strokes, particularly those affecting the brainstem or posterior circulation, can present with less obvious signs such as dizziness, vision changes, or persistent hiccups. These symptoms may occur without the classic one-sided weakness and should be taken seriously, especially if they appear suddenly or alongside other neurological changes. Prompt medical evaluation can be critical for improving outcomes.

Popular Joint Supplement Tied to Faster AD Progression - Glucosamine

 

FYI. Ask your doctors what this means.  They have had 11 years to figure this out. How incompetent are they to have done nothing in 11 years?

• glucosamine (4 posts to March 2015)

• 
  

This research comes to a different conclusion than the latest one below so ask your doctor for EXACTNESS! Maybe age 60 is the cutoff point

The association between regular glucosamine use and risk of dementia

The latest here:

Popular Joint Supplement Tied to Faster AD Progression

Glucosamine, a popular joint-pain supplement, may worsen outcomes in people with mild cognitive impairment (MCI), and a newly identified metabolic pathway involving excessive protein glycosylation could help explain why, new research suggests.

In a large electronic health record analysis, glucosamine use was associated with a 25% higher likelihood of progression from MCI to dementia over 5 years. Experiments in human brain tissue and mouse models suggested that excessive protein glycosylation may contribute to Alzheimer’s disease (AD) progression and that glucosamine supplementation could exacerbate the process by fueling glycan production.

Although preliminary, researchers said the findings point to glycan metabolism as a possible therapeutic target and raise questions about the safety of glucosamine use among patients with established dementia.

“In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias such as Lewy body or frontotemporal dementia. A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse,” senior investigator Ramon Sun, PhD, director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation at the McKnight Brain Institute at the University of Florida, Gainesville, Florida, said in a statement.

Article Key Points

Glucosamine, a common joint supplement, may accelerate Alzheimer's progression by 25% over five years, potentially due to increased protein glycosylation. This raises concerns about its safety for dementia patients, warranting further investigation.

The study was published online on June 9 in Nature Metabolism.

Altered temporal variability-based functional reorganization of brain networks predicts motor outcome after stroke

 Predicting recovery rather than delivering recovery IS COMPLETE INCOMPETENCE!

I take no prisoners in trying to get stroke solved and that means a lot of dead wood needs to be removed. 

Altered temporal variability-based functional reorganization of brain networks predicts motor outcome after stroke

• Guojun Xu,
• Ling Li,
• Qinyang Li,
• Hewei Wang,
• Mingxia Fan,
• Limin Sun,
• Zhiyong Zhao &
• Hongxing Wang 

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract

Background

Dynamic functional connectivity (FC) studies have shown that motor recovery after stroke was associated with functional reorganization of brain networks. However, most previous studies have focused on interregional variability rather than the temporal variability (TV) of specific regions or networks. TV quantifies the dynamic reconfiguration of a region’s or network’s functional connectivity profile over time and reflects neural flexibility.

Purpose

This study investigated functional reorganization in chronic subcortical stroke using TV of brain networks derived from resting-state fMRI.

Methods

Thirty-three patients with left subcortical stroke (LSS), thirty with right subcortical stroke (RSS), and fifty-six age- and sex-matched healthy controls (HCs) were enrolled. Stroke patients underwent resting-state fMRI and Upper Extremity Fugl-Meyer Assessment (UE-FMA) at two time points. TV was computed to characterize dynamic functional connectivity at regional, intra-network, and inter-network levels. Group differences were assessed using one-way ANCOVA with post hoc tests. Linear regression was used to examine associations between TV and motor outcomes. The false discovery rate was used to multiple comparisons correction.

Results

Compared with HCs, both LSS and RSS showed significantly reduced TV in the right frontal-cingulate regions, the somatomotor hand network (SSH), and the connections between SSH and higher-order cognitive networks (all p < 0.05, |Cohen’s d| > 0.49). Increased TV was observed in the left postcentral gyrus, inferior frontal gyrus, cerebellar network (CEN), and somatomotor mouth network (all p < 0.05, |Cohen’s d| > 0.48). Relative to LSS, RSS exhibited additional TV reductions in the right middle occipital gyrus, orbital middle frontal gyrus, default mode network (DMN), and interactions among higher-order cognitive networks (all p < 0.05, |Cohen’s d| > 0.65). Notably, TV in the right opercular inferior frontal gyrus (IFGoperc) (β = 102.69, adjusted p = 6.4 × 10^− 5) and CEN (β = 27.87, adjusted p = 0.011) at the first observation positively correlated with UE-FMA scores at follow-up, with effects modulated by lesion laterality.

Conclusion

TV captures multiscale functional reorganization in chronic subcortical stroke involving motor, cognitive, and sensory networks. TV of the right IFGoperc showed potential as a neuroimaging biomarker for predicting post-stroke motor recovery.

The dilemma of neuroprotection trials in times of successful endovascular recanalization

Never use the word neuroprotection, it has no meaning for survivors. Use the term; neuronal cascade of death; if your doctor tells you they failed to stop the neuronal cascade of death  in the first week resulting in the death of millions to billions of neurons, your correct response would be: 'WHY ARE YOU SO FUCKING INCOMPETENT IN NOT PREVENTING THAT?'

The dilemma of neuroprotection trials in times of successful endovascular recanalization

Antje Schmidt-Pogoda^1†Johannes Kaesmacher^2†Nadine Bonberg^3†Nils Werring¹Jan-Kolja Strecker¹Mailin Hannah Marie Koecke¹Carolin Beuker¹Jan Gralla²Raphael Meier²Heinz Wiendl¹Heike Minnerup^3‡Urs Fischer^4,5‡Jens Minnerup^1*‡

• ¹Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany
• ²University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
• ³Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
• ⁴Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland
• ⁵Department of Neurology, University Hospital Bern, University of Bern, Bern, Switzerland

Background: The “translational roadblock” between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution.

Methods: To verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later.

Results: Our preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%.

Conclusion: Our study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.(Really? You missed all the research that shows continued death of neurons in the penumbra?Why are you still using this milquetoast term? The Rockefeller University in 2008 coined the term, cascade of death; which at least means urgency.)

Introduction

Decades of acute stroke research have come to an unanimous conclusion: “Everything works in animals, but nothing works in people” (1–3). This so called “translational roadblock” between successful animal studies and neutral clinical trials was usually attributed to conceptual weaknesses (4–7). Nonetheless, we hypothesized that intrinsic pathophysiological differences between rodents and humans, i.e., differences in infarct evolution, contribute to translational failures of neuroprotective stroke drugs.

Most animal studies use models of transient middle cerebral artery occlusion (tMCAO). The pharmacological neuroprotective treatment is usually initiated after reperfusion and neuroprotective efficacy is determined by infarct volume assessment (4). This implies that post-reperfusion infarct volume growth is the therapeutic target of neuroprotection in animal studies. Thus, the question arises if and to what extend infarct volume growth is present in human stroke patients. Considering the huge treatment effects of recanalizing therapies, we hypothesized that so called neuroprotective agents can have only limited additional value after complete endovascular recanalization in the majority of patients.

Here, we compare the infarct evolution in rodents with and without neuroprotective treatments with that in human stroke patients with and without successful thrombectomy, and we illustrate why the concept of neuroprotection requires a thorough selection of suitable stroke patients in the clinical setting.

Methods

Data sources

For animal data, we systematically searched Pubmed from the beginning until July 2020 using the terms MRI AND stroke AND animal model AND infarct volume or MRI AND stroke AND rodent AND infarct volume or MRI AND stroke AND mouse AND infarct volume or MRI AND stroke AND rat AND infarct volume. For clinical data, we used a large cohort of stroke patients admitted to the University Hospital Bern (Inselspital) between January 2012 and July 2017.

Study selection and data extraction of animal studies

We included rodent studies that (a) used either transient middle cerebral artery occlusion (tMCAO) or permanent middle cerebral artery occlusion (pMCAO) for stroke induction and (b) provided at least two sequential MRI scans for infarct volume assessment. The first MRI scan had to be after reperfusion but no later than 6 h after stroke onset. The second scan had to be one or two days later. A detailed description of study selection criteria of the systematic review and data extraction is provided in the Supplementary methods. A PRISMA Checklist is also provided in the Supplementary methods.

Data analysis of animal studies

Delayed infarct volume growth was determined by the change in mean infarct sizes between time point 1 and 2 per study [(mean volume at t2/mean volume at t1) × 100–100%].

Selection of stroke patients and documentation of clinical findings

We used a cohort of consecutive stroke patients with clinically suspected large vessel occlusion, who received a primary MRI scan upon admission and at least one follow up-scan one or two days later. We decided to use MRI scans upon admission as baseline scans, because MRI immediately after reperfusion is generally scarce. If compared to MRI scans immediately after reperfusion, MRI scans upon admission overestimate the infarct volume growth rather than underestimate it due to potential infarct volume growth between first scan and successful thrombectomy. In our analyses, a TICI 2b or TICI 3 thrombectomy was regarded as a successful recanalization, thus reflecting the condition in animals with tMCAO, while a TICI 0 to TICI 2a thrombectomy was regarded as an unsuccessful recanalization, thus reflecting the condition in animals with pMCAO. We acknowledge the crucial distinction between recanalization and reperfusion; while recanalization refers to the reopening of the occluded vessel, reperfusion denotes the restoration of blood flow to the affected downstream tissue, which may not automatically ensue following successful recanalization due to various pathophysiological factors.

Data analysis of stroke patients

Infarct evolution in human stroke patients was determined on an individual level by (volume at time point 2/volume at time point 1) × 100–100%. A linear mixed model with random intercepts per patient was conducted to assess the association of time with ln of infarct size. An overall regression line given by the fixed effects of the mixed model is shown in the plot.

Results

Characteristics of included studies and study subjects

Our preclinical meta-analyses included 50 studies from 32 different research groups with 676 animals. A PRISMA flow chart is provided in Figure 1. A table including study details of all studies is provided in the Supplementary Table S1.

Figure 1

Figure 1. PRISMA flow chart illustrating the identification of animal studies.

Our analysis of infarct growth in stroke patients included 107 patients. The mean age was 69 years, the mean NIHSS upon admission was 10, and the mean duration from symptom onset to groin puncture was 5 h.

Infarct growth is the target of neuroprotection in animal stroke, but stroke patients with successful recanalization do not offer this target

To analyze the temporal dynamics of infarct volume progression in animal stroke, we identified stroke studies providing at least two sequential MRI scans, with a first scan within the first six hours after transient middle cerebral artery occlusion and a second scan one or two days later. Among all studies that matched the inclusion criteria as detailed above, 84% reported increasing infarct volumes in untreated animals over the first two days after tMCAO. In untreated animals, the median infarct growth over the first two days after tMCAO was 74% (Figures 2A,B).

Figure 2

Figure 2. Delayed infarct volume growth is the target of neuroprotection in animal stroke, but most stroke patients with successful recanalization do not offer this target. (A,B) Infarct growth after tMCAO in rodents without neuroprotective treatment. (A) Black and green lines connect the mean infarct volumes of untreated animals determined at timepoints 1 and 2 in each individual study. (B) Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was 74%. (C,D) Infarct growth after tMCAO in rodents with neuroprotective treatment. (C) Black and green lines connect the mean infarct volumes of treated animals determined at timepoints 1 and 2 in each individual study. (D) Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was 23%. (E,F) Infarct growth in stroke patients with TICI 2b-3 thrombectomy. (E) Black lines connect the infarct volumes at timepoints 1 and 2 in each patient. The red line represents an overall regression line given by the fixed effects of the mixed model. (B) Each cross represents the infarct volume growth in a patient. The median change in infarct volumes was only 2%.

We next analyzed the effects of neuroprotective treatments on infarct volume progression in animal stroke. To this end, we searched the above data set for studies, in which the effectiveness of neuroprotective treatments was investigated by sequential MRI scans. As expected, our results confirm a powerful treatment effect of neuroprotectants in animal stroke: In treated animals, there was only a small median infarct growth of 23% in the first two days after stroke (Figures 2C,D). Compared to untreated animals, neuroprotective treatments reduced infarct growth to less than a third. These data clarify that delayed infarct growth is the target of neuroprotective treatments in animal stroke.

Considering that neuroprotective treatments with powerful effects in animals have always failed in large clinical trials, we hypothesized that delayed infarct growth might simply not occur in human stroke patients with transient large vessel occlusion. In other words, stroke patients might just not offer a target for neuroprotection. To verify this hypothesis, we used a large dataset of 119 consecutive stroke patients with clinically suspected large vessel occlusion, who were admitted to the Inselspital Bern and received a primary MRI scan upon admission and at least one follow up-scan one or two days later. Among these 119 patients, 51 patients had a TICI 2b or TICI 3 thrombectomy, indicating almost complete reperfusion. In these patients, the median infarct volume increase was only 2% (Figures 2E,F).

Altogether, these findings confirm our intriguing hypothesis that there is no relevant infarct growth after successful recanalization of large artery stroke in human stroke patients, i.e., these patients have no target for neuroprotection.

Infarct growth depends on ischemia duration and recanalization success

Next, we examined to which extent infarct growth depends ischemia duration. Our rodent data suggest a linear relationship between infarct growth and ischemia duration (Figures 3A,B). Regardless of the duration of ischemia, rodents benefited from neuroprotective therapy: With a tMCAO duration of 30–60 min, the median infarct volume growth was reduced from 48% to-16%, with a tMCAO duration of 90–95 min, the median infarct volume growth was reduced from 76 to 32%, and with an ischemia duration of > = 120 min, the median infarct volume growth was reduced from 89 to 21% (Figures 3C,D). In accordance with our animal data, our human data also show an increase in infarct growth depending on the duration of ischemia (Figures 3E,F).

Figure 3

Figure 3. Infarct growth depends on ischemia duration. (A–C) Infarct growth after tMCAO in rodents without neuroprotective treatment. (A) Infarct growth between MRI 1 and MRI 2 based on the duration of ischemia. Each dot represents the mean infarct growth in an individual study. (B) Estimated infarct growth per hour based on the duration of ischemia. Each dot represents an individual study. Assuming a linear growth of infarct volume within the first 48 h, the expected infarct growth per hour can be calculated for ischemia durations between 0 and 2 h using the following formula: 1.62 × t (t: duration of ischemia in hours; t < = 2). This formula is limited to ischemic times between 0 and 2 h. We assume that the curve flattens and is no longer linear with longer ischemic durations, but we cannot estimate this from our available data. (C) Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was 48% after 30–60 min ischemia duration, 76% after 90–95 min ischemia duration and 89% after > = 120 min ischemia duration. (D) Infarct growth after tMCAO in rodents with neuroprotective treatment. Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was-16% after 30–60 min ischemia duration, 32% after 90–95 min ischemia duration and 21% after > = 120 min ischemia duration. (E,F) Infarct growth based on ischemia duration in human stroke patients. (E) Infarct growth between MRI 1 and MRI 2 based on the duration of ischemia. Each dot represents the infarct growth of an individual patient. (F) Assuming a linear growth of infarct volume within the first 48 h, the expected infarct growth per hour can be calculated for ischemia durations between 0 and 2 h using the following formula: 0.26 × t (t: duration of ischemia in hours; t < = 16). This formula is limited to ischemic times between 0 and 16 h. We assume that the curve flattens and is no longer linear with longer ischemic durations, but we cannot estimate this from our available data.

After permanent MCAO, rodents exhibited a median infarct volume growth of 68% (Figures 4A,B). This was reduced to 42% with neuroprotective therapy (Figures 4C,D). Importantly, stroke patients with unsuccessful recanalization (TICI 0-2a) had a meaningful infarct volume growth of 145% (Figures 4E,F). In summary, these data demonstrate that infarct volume growth depends on recanalization success and ischemia duration. Patients with either very late recanalization or unsuccessful recanalization may benefit from neuroprotective therapies.

Figure 4

Figure 4. Infarct growth after permanent large vessel occlusion. (A,B) Infarct growth after pMCAO in rodents without neuroprotective treatment. (A) Black lines connect the mean infarct volumes of untreated animals determined at timepoints 1 and 2 in each individual study. (B) Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was 68%. (C,D) Infarct growth after pMCAO in rodents with neuroprotective treatment. (C) Black and green lines connect the mean infarct volumes of treated animals determined at timepoints 1 and 2 in each individual study. (D) Each cross represents the change in mean infarct volumes in an individual study. The median change in mean infarct volumes was 42%. (E,F) Infarct growth in stroke patients with TICI 0-2a thrombectomy. (E) Black lines connect the infarct volumes at timepoints 1 and 2 in each patient. The red line represents an overall regression line given by the fixed effects of the mixed model. (B) Each cross represents the infarct volume growth in a patient. The median change in infarct volumes was 148%.

Discussion

Our key findings are: first, there is significant infarct volume growth after transient large vessel occlusion in animal stroke models. Second, this delayed infarct volume growth is the target of neuroprotective treatments in animal stroke. Third, most stroke patients with large vessel occlusion have no infarct growth after successful recanalization, i.e., these patients have no target for neuroprotection. Fourth, patients with either very late or unsuccessful recanalization experience meaningful infarct growth, thus offering a potential target for neuroprotection.

Our finding of negligible infarct growth in stroke patients is in line with observations from a recent multicenter clinical trial on the effect of remote ischemic perconditioning on brain infarction growth within the first 24 h after stroke onset (8). In this trial, more than 90% of patients received a recanalizing treatment, infarct volume growth was negligible (34% and 36%) and remote ischemic perconditioning did not have an additional treatment effect (8). Two other studies showed more pronounced infarct volume growth, which appears conflicting at a first glance (9, 10). However, these studies enrolled patients from 2008 until 2013 and from 2011 until 2019, respectively, so that a large proportion of patients were treated with fist-generation devices, which are associated with a higher risk of secondary injury due to thrombus fragmentation and endothelial damage (9, 10). In those patients treated with stent-retrievers, only 14% had substantial infarct volume growth (defined as infarct expansion >11.6 mL) (9).

The rapid expansion of Endovascular Therapy (EVT) facilities and the success of these interventions underscore the relevance of our findings. Our study shows minimal infarct growth in patients with successful recanalization, highlighting the narrowing window for neuroprotective strategies as EVT becomes more prevalent. This shift challenges the translation of neuroprotection from animal models to clinical practice. In light of EVT advancements, our results emphasize the urgent need to adapt neuroprotective research within this new context. Future studies should focus on optimizing neuroprotective approaches in tandem with EVT, underscoring the importance of integrating preclinical and clinical research to enhance stroke treatment efficacy.

It has to be noted that infarct volume growth might be underestimated in our cohort, because we included only patients who were amenable to receive a primary MRI scan, thus excluding unstable patients with a higher likelihood of delayed infarct growth. On the other hand, we used MRI scans upon admission as baseline scans, which, if compared to MRI scans immediately after reperfusion, may overestimate the infarct volume increase due to infarct growth between first scan and successful thrombectomy.

One limitation is that our study focused on large vessel occlusions, and our findings may not directly apply to small infarcts. The rationale for focusing on large occlusions is that the successful neuroprotection studies in rodents primarily used the tMCAO model of stroke, which corresponds to a proximal occlusion of the middle cerebral artery with successful recanalization (i.e., TICI 2b or TICI 3) in human stroke patients. By focusing on large vessel occlusions, we aim to achieve the best possible comparability between animal models and the clinical situation. We acknowledge a limitation in our comparative analysis stemming from the differing criteria for inclusion and assessment between the clinical and preclinical studies. Specifically, while the clinical studies included patients based on successful reperfusion, defined as TICI 2b-3 reperfusion, the animal studies were selected based on successful recanalization without consistent evaluation of effective reperfusion. This discrepancy may contribute to the observed differences in infarct volume growth between the animal models and clinical outcomes. The potential for less effective reperfusion in the animal models despite successful recanalization highlights a critical area for future research and underscores the necessity of rigorous reperfusion assessment in preclinical stroke models. This limitation underscores the complexity of directly comparing preclinical and clinical outcomes and emphasizes the importance of considering the nuances of reperfusion quality in translational stroke research. To better reflect the clinical situation in animal models, some other authors have proposed the establishment of large animal models of stroke. However, besides ethical concerns, there are also purely scientific doubts about whether this can truly achieve better translation, because studies with large animal models tend to have a small sample sizes and heterogeneous results, so that significant findings are difficult to obtain. Furthermore, the future implementation of preclinical multicenter studies will not be feasible with large animal models, as only a few centers with very heterogeneous research focuses have the capability to conduct large animal studies.

While the intraluminal filament model of MCAO is widely accepted and extensively used in preclinical stroke research, we acknowledge its limitations, including variability in the type of filament used and the intravascular events it induces, which may not fully replicate the complex nature of human stroke.

Previously, we identified methodological weaknesses and publication bias as major culprits for the observed efficacy decline of neuroprotective treatments from experimental studies to Phase 3 trials (4). Here, we approached this topic from another perspective and uncovered a fundamental difference in infarct evolution between rodents and humans. How can we explain such wide deviation in infarct evolution between rodents and humans? There are neuroanatomical variations in collateral systems and the proportions between gray matter and white matter (11). For instance, a complete circle of Willis is present in only 10% of C57Bl/6 J mice and Wistar rats were shown to possess particularly thin posterior communicating arteries (12, 13). Insufficient collateral blood supply and limited ability for remodeling after arterial occlusion may thus add to reduced ischemic tolerance and accelerated ischemic cell death in rodents compared to patients. Further, differences in the proportions between grey and white matter volumes may influence vulnerability to delayed ischemic cell death. Notably, the percentage of white matter accounts for 60% in humans, but decreases to 10% in mice (14). Altogether, these differences in neuroanatomical and biochemical prerequisites between species may at least partially explain unequal ischemic vulnerability.

In conclusion, our study reveals a meaningful pathophysiologic difference between animal stroke models and stroke patients: Animals have a huge infarct growth after transient middle cerebal artery occlusion (tMCAO), whereas stroke patients with large vessel occlusion do not have a meaningful infarct growth after successful thrombectomy. Assuming that infarct growth is the target of neuroprotection in animal stroke studies, most stroke patients just do not offer a target for neuroprotection after successful thrombectomy.