Human dental pulp stem cell secretome boosts stroke recovery

And your incompetent? doctor DID NOTHING with this earlier secretome research, right?

Complex "cocktail" in white blood cells has regenerative effect after heart attack or stroke December 2015

The massive incompetence of the complete stroke medical world is mind boggling! 

The latest here:

 Human dental pulp stem cell secretome boosts stroke recovery

Ischemic stroke can leave lasting neurological damage after the initial vascular event, with oxidative stress, neuroinflammation, neuronal death, and disruption of neural connectivity contributing to impaired recovery. Although current interventions provide partial protection, their ability to prevent delayed neuronal injury remains limited, highlighting a major barrier to functional recovery.

The human dental pulp stem cell (hDPSC) secretome contains extracellular vesicles, growth factors, antioxidant enzymes, and immunomodulatory proteins and may offer a potential cell-free therapeutic approach. However, understanding of their therapeutic impact on delayed neuronal injury after reperfusion is limited.

Now, a study led by Professor Won-Jae Kim from the Stem Cell Secretome Research Center, Department of Oral Physiology, School of Dentistry, Chonnam National University, South Korea, investigated whether the hDPSC secretome could improve functional recovery in a photothrombotic mouse model and examined the biological processes associated with its effects. Their study was made available online on July 23, 2026, in the journal Advanced Science.

By utilizing the bioactive factors secreted by stem cells rather than the cells themselves, secretome-based therapy overcomes the classic hurdles of cell transplantation, such as poor cell survival, immune rejection, and tumorigenesis. We wanted to investigate if the hDPSC secretome could be deployed as a safe, supportive treatment to mitigate secondary brain injury, modulate neuroinflammation, and accelerate neural repair post-stroke."

Professor Won-Jae Kim, Stem Cell Secretome Research Center, Department of Oral Physiology, School of Dentistry, Chonnam National University, South Korea

The study identified 299 proteins uniquely present in the hDPSC secretome, which were majorly associated with extracellular vesicles, immunomodulation, neuroprotection, angiogenesis, apoptosis regulation, and oxidative-stress resistance. Several of these proteins were particularly associated with antioxidant defense. While SOD2, GSR, and GSTP1 were tied directly to the brain's antioxidant defense network, proteins like GRN, CSF1, and LRP1 emerged as key regulators of microglial phenotype regulation.

The hDPSC secretome improved microglial cell viability, reduced oxidative stress, and restored mitochondrial function in the in vitro study. It restored expression of the mitochondrial fusion protein Mfn2 and antioxidant enzyme SOD1 while reducing hypoxia-associated HIF-1α expression. Additionally, hDPSC secretome suppressed microglial migration and inflammation, promoting a shift from the pro-inflammatory M1 phenotype toward the pro-healing M2 phenotype.

Stem Cell Therapy Shows Promise for Stroke Recovery

 The promise has been out there for well over a decade, WHOM will actually solve the problem? NO leadership and NO strategy is the result of our fucking failures of stroke associations!

• stem cells (409 posts to April 2011)

Stem Cell Therapy Shows Promise for Stroke Recovery

University of Miami Miller School of Medicine

Researchers from the University of Miami Miller School of Medicine and collaborating institutions have published a comprehensive review examining the rapidly evolving field of intra-arterial stem cell therapy for ischemic stroke, highlighting its potential to improve recovery for patients who continue to face disability despite major advances in stroke treatment.

Published in the American Heart Association Journal Stroke: Vascular and Interventional Neurology, the review, titled "Progress in Intra-arterial Stem Cell Therapy for Ischemic Stroke – A Review," examines decades of preclinical and clinical research and outlines a roadmap for translating regenerative therapies from the laboratory to the bedside.

Ischemic Stroke, in which blood supply to a part of the brain is cut off by suddenly by a clot blockage, remains one of the leading causes of death and long-term disability worldwide. While clot-busting medications and mechanical thrombectomy have transformed care for acute ischemic stroke, many patients are left with significant neurological deficits despite successful restoration of blood flow. The authors argue that stem cell therapies delivered directly into the brain's circulation via minimally invasive and widely available catheter angiographic techniques may complement existing treatments. The stem cells targeted this way to the stroke injured brain area work by promoting brain repair, reducing inflammation, and enhancing recovery.

"Mechanical thrombectomy has revolutionized stroke treatment, but half of the treated or more patients still do not regain full independence," said Dileep R. Yavagal, M.D., professor of clinical neurology and neurosurgery at the University of Miami Miller School of Medicine and senior author of the review. "Stem cell therapy represents a promising strategy to help the brain recover after injury and may become an important next step in improving outcomes(NOT GOOD ENOUGH!) for stroke patients."

(Likely a much better approach to full recovery is stopping the 5 causes of the neuronal cascade of death in the first week and thus saving hundreds of millions to billions of neurons! So you aren't even thinking of this properly!)

A Targeted Approach

Stem cells can be delivered through several different routes and optimal route in Stroke treatment is not yet established. The review focuses on intra-arterial delivery, an approach in which stem cells are infused directly into arteries supplying the injured region of the brain. Unlike intravenous administration, in which much of the cells are trapped in organs such as the lungs and liver, intra-arterial delivery into the affected artery allow a greater concentration of therapeutic cells to reach stroke-affected tissue. Surgical approaches such through a small hole in the skull are more invasive.

Researchers note that intra-arterial delivery is particularly attractive because it can potentially be performed during the same minimally invasive endovascular procedures and techniques used now as standard of care treatment, mechanical thrombectomy, avoiding the need for a new surgical access or additional intervention.

Preclinical studies, including from Dr. Yavagal's laboratory at the University of Miami Miller School of Medicine Interdisciplinary Stem Cell Institute, reviewed by the authors demonstrate that stem cells may reduce inflammation, promote formation of new blood vessels, support neural repair, and improve neurological outcomes following stroke. Multiple early-stage clinical trials have also established the feasibility and safety of stem cell administration across several delivery routes.

Strong safety record, more research needed

The review analyzes more than two decades of clinical development and notes that more than 40 randomized clinical trials have investigated stem cell therapies for stroke via many different routes of delivery. While safety has been consistently demonstrated, evidence for definitive functional benefit remains under investigation. Several ongoing studies are working to determine optimal cell type, dosing, timing, and patient selection strategies.

"The safety of IA stem cell therapy has been established by several preclinical and clinical studies and will continue to remain a critical endpoint for all future studies," said Roshni Thakkar, Ph.D., co-first author and research assistant professor in the Department of Neurology at the University of Miami. "The next challenge that the field is taking on is to identify the right cells, the right dose, the right patients, and the right time to intervene in order to maximize stroke recovery."

The authors emphasize that future studies should integrate advanced imaging, biological markers, and immune profiling to better understand how stem cells interact with the post-stroke brain and to identify patients most likely to benefit.

"Regenerative medicine has the potential to fundamentally reshape stroke treatment," said Nadia McMillan, M.D., Ph.D., co-first author, senior neuro-endovascular fellow and instructor . "The goal is not only to save brain tissue during a stroke but to help patients regain function and quality of life afterward."

Looking toward the future

According to the review, emerging therapies may eventually include bioengineered stem cells, extracellular vesicles and exosomes, and combination approaches that pair thrombectomy with regenerative treatments. Continued advances could ultimately transform stroke care from a model focused primarily on restoring blood flow to one that also actively promotes brain repair and recovery.

The authors conclude that while significant challenges remain, ongoing clinical trials and rapid advances in regenerative neuroscience provide reason for optimism that stem cell-based therapies may one day become an important adjunct to standard stroke treatment and achieve an outcome free of disability for the vast majority of stroke patients.

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Tags: regenerative medicine , america , investigation , american , Administration , Miami , biological , neuroscience , clinical trials , neurosurgery , University of Miami , blood vessels , inflammation , cell therapy , American Heart Association , quality of life

Cannabidiol Drives Efficient Neural Differentiation of Human Wharton’s Jelly Mesenchymal Stem Cells: A Small-Molecule Approach for In Vitro Neurogenesis

Will your competent? doctor conclude that this is worth writing a protocol on to get you better recovery? Or, WILL NOTHING BE DONE, LIKE USUAL?

Of course your incompetent? doctor won't get further research going!

 Cannabidiol Drives Efficient Neural Differentiation of Human Wharton’s Jelly Mesenchymal Stem Cells: A Small-Molecule Approach for In Vitro Neurogenesis

  Erfan Motalebzadeh 1 , Akram Tajik 2 , Raheleh Halabian 3 , Nafiseh Abbasabadi 4, Hanieh Ahmadi 5, Ali Salimi 6* 1 Department of Biology, Basic Science Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 3 Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 4 Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran 5 Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran 6 Tissue Engineering and Regenerative Medicine Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Corresponding Author: Ali Salimi, PhD, Associate Professor, Tissue Engineering and Tissue Engineering and Regenerative Medicine Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. Tel: +989128596570, E-mail: salimiali@bmsu.ac.ir Received August 11, 2025; Accepted November 5, 2025; Online Published June 30, 2026 

 Abstract 

 Introduction: 

Over the past decade, research on small molecules such as cannabidiol (CBD) has expanded due to their ability to modulate biological pathways through protein interactions. Understanding how mesenchymal stem cells (MSCs) differentiate into neural-like cells is crucial for developing effective therapies for neurological disorders. This study aimed to investigate the efficacy of cannabidiol, as a cost effective small-molecule inducer, in promoting the neural differentiation of human Wharton’s jelly MSCs (hWJ-MSCs) in vitro and to determine the optimal non-cytotoxic dose for this purpose. 

 Materials and Methods: 

The optimal CBD dose (5 μg/ml) was first determined using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. To evaluate neural differentiation potential, the expression of neural marker genes, MAP-2, NSE, Oligo-2, β-tubulin III, and GFAP, was assessed by real-time PCR at 7 and 14 days’ post-induction. 

 Results: 

The results demonstrated significant upregulation of neural marker genes at 7 and 14 days after CBD treatment, confirming successful induction of neural differentiation. 

 Conclusions: 

The designed protocol is highly effective and efficient for inducing neural differentiation. Further in vivo studies using biocompatible scaffolds are necessary to elucidate the underlying mechanisms and therapeutic implications of these findings. 

 Keywords: 

Cannabidiol, Small Molecules, Wharton’s Jelly Mesenchymal Stem Cells, Neural-Like Cells Citation: Motalebzadeh E, Tajik A, Halabian R, Abbasabadi N, Ahmadi H, Salimi A. Cannabidiol Drives Efficient Neural Differentiation of Human Wharton’s Jelly Mesenchymal Stem Cells: A Small-Molecule Approach for In Vitro Neurogenesis. J Appl Biotechnol Rep. 2026;13(2):2080-2088. doi:10.30491/jabr.2025.540602.1903

Inflammation Forces Brain Stem Cells to Halt Neurogenesis

 How EXACTLY  will your competent? doctor prevent this inflammation? You need neurogenesis to recover according to your doctor; SO THERE BETTER BE A SOLUTION!

Inflammation Forces Brain Stem Cells to Halt Neurogenesis

Summary: A new study demonstrated that introducing inflammatory signaling molecules directly into human hippocampal stem cells brings new neuron production to a dead stop. Instead of simply dying or becoming damaged, the brain’s neural stem cells actively abandon their regenerative responsibilities, transforming into an “immune alert” state that actively fuels localized neuroinflammation.

Key Facts

• The Cytokine Intrusion: The team analyzed the behavior of cytokines, specialized chemical signaling proteins released by the body during immune threats, such as severe viral infections. While transient cytokine spikes help clear out acute sickness, sustained high levels are a classic hallmark of devastating chronic inflammation.
• The TNF-α Standstill: When researchers exposed human hippocampal stem cells to a specific pro-inflammatory cytokine called Tumor Necrosis Factor alpha (TNF-α), the cellular birth pipeline froze. The stem cells completely ceased differentiating into mature, functional neurons.
• The “Immune Alert” Takeover: To the shock of the investigators, the stem cells weren’t merely passive casualties of chemical stress. Instead, they actively assumed a hostile, immune-supportive behavior, pumping out high-alert chemical signals designed to recruit inflammatory T cells straight into the brain’s delicate learning centers.
  
• The Type I Interferon Accidental Route: By mapping the molecular cascade, the team identified a highly unexpected signaling pathway driving this cellular hijack: Type I Interferons. These molecules are traditionally recognized as the body’s first-line defensive shield against viral replication, but here they inadvertently act as the executioner of neurogenesis.
• Reversing the Damage: In a major therapeutic triumph, the KCL team introduced an existing therapeutic antibody designed to block Type I Interferon signaling. The intervention successfully reversed the damage, shutting down the recruitment of inflammatory T cells and completely restoring the stem cells’ capacity to regenerate fresh, healthy neurons.
• A Diagnostic Bridge for Long-Syndromes: This discovery provides an invaluable clinical explanation for the persistent cognitive impairments, “brain fog,” and mood disorders reported by patients recovering from aggressive viral infections, navigating major depressive disorders, or entering the early stages of Alzheimer’s disease.

Source: King’s College London

The King’s College London study, published in Nature Communications, offers insight into how long-term inflammation may contribute to cognitive decline in disorders such as Alzheimer’s disease, ageing, depression, and the lingering neurological effects of viral infections.

The scientists discovered that adding a molecule, that is involved in the inflammatory response, to stem cells from the hippocampus prevents the development of new neurons. The formation of new neurons in this region, known as hippocampal neurogenesis, is essential for learning, memory and mood regulation. It is one of the few parts of the human brain where new neurons are made in adults. Altered adult hippocampal neurogenesis is associated with ageing, neurodegeneration, and mood disorders such as depression.

Scientists Reverse Stroke Damage Using Stem Cells in Breakthrough Study

This is different than all the other stem cell research I've seen where stem cells aren't even monitored after transplantation and exosomes are the reason for improvement!  But why go thru all the trouble of stem cells if exosomes are the reason for the benefits? Which must be why no one seems to be monitoring stem cell survival. Ask your competent? doctor for clarification!

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations 

The latest here:

Scientists Reverse Stroke Damage Using Stem Cells in Breakthrough Study

Scientists have discovered that transplanted stem cell-derived brain cells may do far more than simply survive after a stroke.

A stem cell treatment helped mice recover from strokes by rebuilding damaged brain connections, restoring blood vessels, and improving movement, according to new research from the University of Zurich and the University of Southern California. The findings raise hopes that future therapies could one day repair stroke damage that is currently considered permanent.

Stroke remains one of the world’s leading causes of long-term disability. When blood flow to part of the brain is cut off, oxygen-starved cells die within minutes. Unlike skin or bone, the brain has only a limited ability to replace lost tissue, leaving many survivors with lifelong paralysis, speech problems, or memory loss.

Scientists have spent years searching for ways to help the brain rebuild itself. In the new study, researchers used neural progenitor cells, early-stage cells capable of developing into different types of brain tissue. The cells were created from induced pluripotent stem cells, which are adult human cells reprogrammed into a stem cell-like state.

The team transplanted these cells into the brains of mice one week after a stroke. That timing turned out to be critical. Earlier transplants survived poorly because the injured brain was still overwhelmed by inflammation and toxic chemical signals. Waiting several days allowed conditions to stabilize enough for the transplanted cells to take hold.

What happened next surprised the researchers.

New Neurons and Rebuilt Connections

Over five weeks, the transplanted cells survived, spread through nearby brain tissue, and matured mostly into functioning neurons. Many became GABAergic neurons, specialized inhibitory brain cells that help regulate neural activity and are heavily depleted after stroke. These cells are essential for balancing brain signaling, preventing excessive excitation, and coordinating movement.

Stem cell therapy for ischemic stroke: neuroimaging approaches and evidence from a systematic review

But why go thru all the trouble of stem cells if exosomes are the reason for the benefits? Which must be why no one seems to be monitoring stem cell survival.

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations 

The latest here:

 Stem cell therapy for ischemic stroke: neuroimaging approaches and evidence from a systematic review

Bin Jiang^1*Moss Zhao²Elizabeth Tong¹Yongkai Liu¹Ates Fettahoglu¹Wen-Kai Weng³Michael E. Moseley¹Max Wintermark⁴Gary K. Steinberg²Greg Zaharchuk¹

• ¹Department of Radiology, School of Medicine, Stanford University, Stanford, CA, United States
• ²Department of Neurosurgery, School of Medicine, Stanford University, Stanford, CA, United States
• ³Department of Medicine - Med/Blood and Marrow Transplantation, School of Medicine, Stanford University, Stanford, CA, United States
• ⁴Department of Neuroradiology, MD Anderson Center, The University of Texas, Houston, TX, United States

Purpose: Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery.

Methods: A systematic search was conducted in 5 databases in July 2025. They were included if neuroimaging analysis, regardless of cell source, route administration or dosage were reported. The level of evidence and risk of bias were assessed using the ROB-2 or ROBINS-I tool. Imaging data from all included articles were extracted, and randomized-effect meta-analyses were performed when two or more outcomes were available for any reported imaging parameter.

Results: Thirty articles were included in the systematic review, of which four were eligible for meta-analysis. Meta-analysis of subacute stroke patients revealed no significant differences in infarct volume reduction at 3 months (SMD = −0.50; 95% CI: −1.15 to 0.51; p = 0.13; I² = 63%) or 1 year (SMD = −1.02; 95% CI: −3.63 to 1.60; p = 0.45; I² = 92%) between treatment and control group. Chronic stroke patients exhibited less overall volume loss. There was a trend toward improved white matter recovery and motor cortex activity, reflected in increased DTI and fMRI parameters. SPIO-labeled autologous stem cells recently proved safe in patients, with T2* imaging showing engraftment and migration.

Conclusion: Advanced neuroimaging offers a valuable non-invasive tool for assessing the effects of stem cell therapy in ischemic stroke. However, substantial heterogeneity in imaging protocols and reporting limits cross-study comparisons. Standardization of neuroimaging methodology is essential to advance future research and clinical translation.

Introduction

Stroke remains one of the leading causes of death and long-term disability worldwide. Among its subtypes, ischemic stroke accounts for the vast majority of cases, arising from obstruction of cerebral blood flow and subsequent brain tissue damage. The growing global burden is striking: from 1990 to 2019, the incidence of ischemic stroke increased by 70% and prevalence by over 100%, with parallel rises in mortality and disability (1). These statistics underscore the urgent need for more effective therapeutic strategies.

Currently, the most effective treatments for ischemic stroke are reperfusion-based interventions, including intravenous thrombolysis and endovascular therapy (EVT). While these approaches can restore blood flow and improve outcomes, their clinical application is limited by narrow therapeutic windows, strict eligibility criteria, and incomplete functional recovery in many patients (2). As a result, a substantial proportion of stroke survivors are left with persistent neurological deficits, highlighting the unmet need for restorative therapies that extend beyond the acute treatment window.

Stem cell therapy has emerged as a promising approach in this context. Building on the 2012 Nobel Prize–winning discovery that somatic cells can be reprogrammed into pluripotent stem cells, preclinical and clinical studies have explored the potential of stem cells to enhance brain repair after ischemic stroke. These studies suggest that stem cells may exert beneficial effects through multiple mechanisms, including promoting neurogenesis, angiogenesis, and synaptic plasticity, as well as modulating neuroinflammation and immune response (3–5). Clinical trials to date have demonstrated safety and feasibility, with early signals of efficacy across different stem cell types, transplantation routes, and stages after stroke onset (6–9).

Despite these advances, critical challenges remain in optimizing stem cell therapy for stroke, particularly in objectively assessing therapeutic effects in the human brain. Neuroimaging offers tools to address this need, providing noninvasive biomarkers of structural and functional brain changes. Techniques such as diffusion tensor imaging (DTI), functional MRI (fMRI), perfusion imaging, and positron emission tomography (PET) can reveal the mechanisms of action, monitor brain repair, and potentially predict clinical outcomes. While prior reviews have summarized stem cell mechanisms, delivery methods, and safety, comparatively little attention has been given to the role of neuroimaging in this field (2, 10–14).

The aim of this systematic review is therefore to synthesize current evidence on structural and functional neuroimaging of stem cell therapy in ischemic stroke. By focusing on imaging biomarkers, we highlight how neuroimaging contributes to understanding treatment mechanisms, evaluating efficacy, and guiding the future development of regenerative therapies for stroke patients.

Methods

Ethics approval by an Institutional Review Board (IRB) was not required for this systematic review.

Protocol and registration

The search strategy and written methodology were developed with the assistance of the medical librarians, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (15), the Peer-Review of Electronic Search Strategies (PRESS) (16), the National Academies (IOM) Standards for Systematic Reviews (17), and the Cochrane guidelines (18).

Inclusion and exclusion criteria

Studies were included if they were published in a peer-reviewed journal, evaluated ischemic stroke in an adult population, administered a specific type of stem cells or stimulating factors for stroke, and included results based on one or more evaluations of functional imaging parameters, including MRI or PET (Table 1). Exclusion criteria were studies that were not full research articles, animal studies, dissertations, or review articles. Additionally, studies focusing on populations with hemorrhagic stroke or strokes from sickle cell or moyamoya diseases were excluded. This selection was chosen to enhance the focus on imaging related to arterial ischemic infarcts.

Table 1

Table 1. Inclusion and exclusion criteria for studies identified in the search (PICOS).

Information sources and search strategy

MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials and Web of Science were searched by a medical librarian (EW). To identify any missing reports, we also hand-searched the references lists from included studies and identified articles meeting the inclusion criteria, contacting authors and experts, and examining related articles in PubMed and Google Scholar. An updated search was conducted in July 2025. Complete, reproducible search strategies for each database are provided in the Supplementary materials.

Study selection and data extraction

All titles, abstracts, and full manuscripts underwent review by two unique individuals within the authorship team, utilizing Covidence systematic review software. In cases of discrepancies, two authors (BJ, MZ) conducted a joint review to reach a final decision regarding study inclusion. To enhance transparency, the predefined PICOS-based inclusion and exclusion criteria (Table 1) were applied consistently throughout title/abstract and full-text review. After full-text screening, we collected the data using a data extraction form. Data collection included: stage of ischemic stroke (acute [<7 days], subacute [1 ~ 12 weeks] or chronic [>3 months]), route, dosage, and type of stem cells introduced, baseline NIHSS, the number of subjects in the intervention and the control group (if present), infarct size and how it was reported (volume, percentage, and etc.), DTI parameters (FA, MD, and etc.), functional MRI, PET changes, and other imaging parameters (such as SPIO labeled T2*).

Risk of bias assessment and level of evidence

Two authors (BJ, YL) evaluated the risk of bias using the ROB-2 (Cochrane risk-of-bias tool) for the randomized control studies (19), and ROBINS-I (Risk of Bias in Non-Randomized Studies of Interventions) tool for non- randomized control studies (20). The following domains were assessed: confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, selection of reported results, and overall risk of bias. The risk of bias was then classified as high, moderate, or low according to the ROB-2 and ROBINS-I tool. The corresponding author was contacted to retrieve missing data. To grade the overall strength of evidence from the included studies, the level of evidence of each included study was assessed by The Oxford Centre for Evidence-Based Medicine Levels of Evidence and scored accordingly (CEBM) (21).

Reporting bias assessment

If at least 10 studies were available for an outcome, we planned to assess reporting bias using funnel plots.

Statistical analysis

We employed a random-effects meta-analysis to combine the study results. Meta-analyses were conducted using Review Manager version 5.4 software (RevMan 2020). For continuous variables, we computed the standard mean difference (SMD) and 95% confidence interval (CI). In cases where numerical outcome data were not directly reported in the original publications, graphical data were extracted. We obtained these values either by contacting the corresponding authors or, when necessary, by digitizing published figures using Web Plot Digitizer¹ (22). This ensured inclusion of studies that otherwise lacked extractable numerical data. Heterogeneity was quantified with the I² statistic, with values of 25, 50, and 75% considered low, moderate, and high, respectively. A two-tailed p value < 0.05 was considered statistically significant.

Results

Search results

A total of 3,838 articles from 5 databases were initially identified. After removing duplicates, 2,685 articles remained. Full-text review was completed on 106 studies, and 30 studies were included in this review (Figure 1). Studies were excluded for the following reasons: (1) not peer-reviewed (n = 45); (2) no imaging to outcome analysis or insufficient imaging data (n = 15); (3) ineligible population (n = 11); (4) non-English (n = 3); (5) wrong intervention (n = 1); (6) wrong indication (n = 1).

Figure 1

Figure 1. PRISMA flowchart illustrating the process of selecting studies included.

Characteristics and quality of evidence of included studies

Of the 30 included studies, 22 were clinical trials, with 8 studies involving sub-analyses of the same study. These studies were conducted in various regions: 4 in North America, 5 in Europe, 12 in Asia, and 1 in Africa (Table 2). All studies incorporated MRI or PET. Among them, 16 studies compared infarct sizes between baseline and the latest available follow-up based on T1-weighted images, 6 included the identification of abnormal high signals on T2 FLAIR images immediately after treatment, 9 included analysis of DTI images, 4 involved functional MRI analysis, 2 studies analyzed perfusion MRI changes, and 5 included PET analysis.