28.05.2026 Stroke is not just a blocked vessel and a race against time. A new study involving Dr. Marcin Tabaka from the International Centre for Translational Eye Research (ICTER) shows that after a stroke, the brain activates its own mechanisms to “patch up” damaged blood vessels.
Ischemic stroke is one of those conditions where modern medicine quite literally fights against time. Minutes determine the fate of neurons, hours shape the extent of damage, and days and weeks decide whether a patient will return to independent life. The scale of the problem is enormous. According to the World Health Organization (WHO), nearly 12 million new strokes occur worldwide every year. It remains one of the leading causes of death and long-term disability in adults.
A stroke often does not kill immediately. Instead, it leaves patients with paralysis, aphasia (speech impairment), and difficulties with memory, concentration, and planning. In Poland alone, the number of cases is estimated at around 90,000 annually, and with an aging population, this burden will continue to grow, placing increasing pressure on healthcare systems and long-term care.
In public discourse, stroke is often reduced to a simple narrative: a blocked vessel, rapid intervention, restored blood flow. Clinicians, however, have long known that this is only the beginning. Even patients in whom blood flow is successfully restored often experience neurological deterioration in the following days. The source of this paradox lies deeper – at the level of microcirculation and the barrier that separates the brain from the bloodstream.
A new study Adult leptomeningeal vestigial neural crest-derived multipotent cells promote vascular repair after stroke published in Cell Reports, co-authored by Dr. Marcin Tabaka from the International Centre for Translational Eye Research (ICTER) at the Institute of Physical Chemistry of the Polish Academy of Sciences, sheds light on this less visible stage of the disease – the moment when the brain attempts to repair damaged vessels on its own and limit further injury.
Acute treatment is not the end of the story
In acute ischemic stroke, the primary goal is to restore blood flow in the blocked vessel as quickly as possible. This is typically achieved through intravenous thrombolysis – a pharmacological treatment that dissolves the clot – administered within the first 4.5 hours after symptom onset. In patients with large vessel occlusion, mechanical thrombectomy is increasingly used, a minimally invasive procedure that physically removes the clot.
Thanks to advances in imaging, particularly perfusion CT and MRI, the treatment window for thrombectomy can be extended to 24 hours in selected patients, provided that some brain tissue remains salvageable.
However, reopening the vessel does not automatically restore the brain to normal function. One of the most critical – yet often overlooked – aspects of stroke is damage to the blood-brain barrier (BBB). This highly specialized structure, formed by endothelial cells and their tight junctions, acts as a precise biological filter under normal conditions. It protects the brain from toxins, inflammatory cells, and an uncontrolled influx of plasma proteins.
After a stroke, this barrier becomes compromised. Inflammatory factors enter the brain tissue, edema develops, and secondary injury can worsen neurological deficits. This stage – already after successful reperfusion – represents a “second phase” of stroke. It is precisely this phase that became the focus of the study involving Dr. Tabaka.
The meninges take on a new role
The researchers turned their attention to structures that have long remained on the margins of stroke research: the arachnoid mater and pia mater – the inner layers of the meninges. These thin membranes, closely adhering to the brain surface, have traditionally been viewed as passive protection and structural support for blood vessels. The new findings suggest a much more active role.
Within the meninges, the researchers identified a small population of cells derived from the neural crest – an embryonic structure that gives rise to a remarkably diverse range of tissues. Neural crest cells contribute to melanocytes (pigment cells), components of the peripheral nervous system, the adrenal medulla, and parts of the craniofacial skeleton. Because of this versatility, the neural crest is sometimes referred to as a “fourth germ layer.”
It was previously believed that cells with such developmental potential either disappear or lose their plasticity after embryogenesis. This study suggests that remnants of these cells persist in the adult brain – and, importantly, can be reactivated in response to acute injury.
A reserve that awakens after a stroke
Following ischemic stroke, these dormant cells begin to migrate from the meninges toward the damaged cortex. They localize near blood vessels and participate in their stabilization. They do not regenerate neurons or reverse the infarct, but they strengthen vessel walls and help restore the integrity of the blood-brain barrier. In animal models, this translated into reduced leakage of the barrier and improved neurological outcomes.
“What is particularly striking is that the brain reaches back to very early developmental mechanisms to cope with acute injury. This is not about dramatic regeneration, but about stabilization – and that stabilization may determine how well patients function after stroke,” says Dr. Marcin Tabaka from ICTER.
The researchers also identified the mechanism guiding these cells to the site of injury. A key role is played by chemical signals produced by damaged endothelial cells. These signals act as biological cues, attracting cells equipped with the appropriate receptors and directing them precisely to where the blood-brain barrier needs repair.
When this signaling pathway was experimentally blocked, significantly fewer repair cells reached the damaged vessels. The blood-brain barrier remained more permeable, and the animals performed worse in neurological tests. This demonstrates that the process is not passive, but tightly regulated.
One of the key molecular “tools” used by these cells is pleiotrophin (PTN), a signaling protein that supports vascular integrity. In laboratory conditions, PTN improved the survival of endothelial cells after ischemia and strengthened their intercellular junctions. In animal models, its activity was associated with reduced damage to the blood-brain barrier.
What did the ICTER team contribute?
In this project, the ICTER team was responsible for the bioinformatics component, based on the analysis of single-nucleus RNA sequencing data (snRNA-seq). Their work involved processing and integrating large-scale transcriptomic datasets comprising more than 100,000 cell nuclei collected at different time points after stroke. This enabled the identification and annotation of cell clusters and, critically, the detection of a rare population of meningeal cells with a neural crest-like signature.
The team also conducted analyses of cellular state dynamics, including RNA velocity – a method that allows prediction of the direction of cell state changes based on transcriptional activity. These analyses showed the transition of these cells toward perivascular phenotypes following stroke. In parallel, ligand-receptor interaction analyses were performed, highlighting key signaling axes such as CXCL12-CXCR4 and the role of secreted factors. Importantly, the integration of snRNA-seq data with spatial transcriptomics made it possible to map these gene expression signatures to specific anatomical locations within the injured brain tissue.
A new way of thinking about stroke
The authors emphasize that this is a preclinical study and does not provide an immediate therapeutic solution for patients. However, it shifts the focus in how stroke is understood – from an exclusive emphasis on restoring blood flow to a broader question of what happens afterward, as the brain attempts to regain balance and limit damage.
“If we learn how to understand and support these endogenous repair mechanisms, we may be able to improve patient outcomes – even when the window for classical treatment has already closed,” Dr. Tabaka concludes.
Yoshihiko Nakamura, Takafumi Nakano, Lluis Alzamora-Llull, Ji-Hyun Park, Masayoshi Tanaka, Ester Licastro, Damian Panas, Shin Ishikane, Dong-Bin Back, Gen Hamanaka, Wenlu Li, Elga Esposito, Yi Zheng, Bum Ju Ahn, Violeta Durán-Laforet, Rakhi Desai, Ikbal Sencan, Klaus Van Leyen, Sava Sakadžić, Evan Y. Snyder, Marcin Tabaka, Kazuhide Hayakawa (2026). Adult leptomeningeal vestigial neural crest-derived multipotent cells promote vascular repair after stroke. Cell Reports.
DOI: https://doi.org/10.1016/j.celrep.2025.116747
Author: Scientific Editor Marcin Powęska
