Mechanical thrombectomy has transformed the treatment of acute ischemic stroke caused by large vessel occlusion. Beyond restoring blood flow, however, the procedure also creates a rare opportunity to study human stroke biology in real time. By collecting blood and clot samples directly during thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) provides a unique window into the molecular environment of the ischemic brain during the earliest stages of stroke.
In this TSE interview, Dr. Keith Pennypacker discusses how BACTRAC was developed, what makes the platform uniquely suited for translational stroke research, and how its findings may help advance precision medicine approaches for stroke recovery.
- Can you briefly introduce the BACTRAC platform and what makes it unique in the study of stroke?
The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) was established nearly a decade ago with the goal of collecting biological samples directly from patients during mechanical thrombectomy for acute ischemic stroke. During the procedure, intracranial blood is obtained from the site of the vessel occlusion, along with systemic arterial blood and the retrieved clot. Blood samples are immediately processed, with plasma separated from the cellular pellet and stored for future analyses.
To date, plasma samples have been studied for arterial blood gases, electrolytes, proteomics, extracellular vesicles, short-chain fatty acids, and microRNAs. Cellular pellets have been analyzed using inflammatory transcriptomics approaches. Future investigations will examine DNA methylation, single nucleotide polymorphisms, and clonal hematopoiesis of indeterminate potential (CHIP). Comprehensive clinical data—including demographics, comorbidities, imaging findings, treatments, and outcomes—are collected for every patient.
By integrating biological and clinical data using advanced statistical methods and machine learning approaches, BACTRAC seeks to identify predictors of cognitive and functional recovery, uncover novel therapeutic targets, and facilitate reverse translation into experimental models. What makes BACTRAC unique is its focus on obtaining biological samples directly from patients with large vessel occlusion stroke at the time of thrombectomy, providing an unprecedented window into the molecular environment of the ischemic brain during the acute phase of stroke.
2. What motivated your team to collect samples directly during thrombectomy, and how has that shaped the questions you are able to ask?
When BACTRAC was conceived, no studies had examined intracranial blood obtained directly from the ischemic territory during an acute stroke. We recognized that this blood could provide unique insight into the molecular events occurring at the site of injury and reveal the earliest biological responses triggered by vessel occlusion.
By studying intracranial blood in human patients, we can investigate the inflammatory and metabolic pathways that contribute to tissue damage, edema formation, and long-term impairments in function and cognition. Identifying these early molecular signals provides opportunities to discover therapeutic targets that could interrupt harmful downstream processes before irreversible injury occurs. This approach has allowed us to ask questions that were previously impossible to address in human stroke patients and has helped bridge the gap between experimental models and clinical disease. While animal models are crucial to understanding mechanisms and testing novel therapies, our bedside-to-bench approach empowers us to study stroke in real-time in human beings.
3. What have been some of the most interesting or unexpected insights from the study so far?
One unexpected finding was that the pH of ischemic intracranial blood does not significantly differ from that of systemic arterial blood. Despite substantial reductions in oxygen levels within the ischemic territory, the blood appears capable of maintaining acid-base balance. This suggests a remarkable resilience of the circulatory system to hypoxic stress during the acute phase of stroke.
Another surprising observation was the activation of a T-helper 2 (Th2) inflammatory response within ischemic blood. Th2 signaling is traditionally associated with allergic responses and parasitic infections, yet we found that several Th2-associated cytokines were strongly associated with infarct size and cerebral edema. These findings suggest that previously underappreciated immune pathways may play an important role in stroke pathophysiology.
We have also identified important regional differences in the biological response to stroke. Because many BACTRAC participants come from Appalachian communities—regions that experience some of the most significant health disparities in the United States—we observed that systemic inflammatory responses differ between Appalachian and non-Appalachian patients. Furthermore, the expression of dementia-related biomarkers during stroke varies by geographic region. These findings suggest that environmental, socioeconomic, and cultural factors influence the molecular response to stroke and highlight the need for more personalized approaches to treatment that account for demographic characteristics, comorbidities, and social determinants of health.
4. How do you see BACTRAC contributing to our broader understanding of stroke biology and patient outcomes?
Historically, stroke research has relied heavily on experimental rodent models. While these models have provided important mechanistic insights, they have not translated into many effective therapies for patients. BACTRAC addresses this gap by studying biological processes directly in human stroke patients during the acute phase of disease.
Our findings are providing new insights into the earliest molecular events occurring within ischemic blood and are helping identify potential therapeutic targets that could be used alongside thrombectomy. In addition, the integration of biological and clinical data is enabling the development of more comprehensive models to predict functional recovery, cognitive outcomes, and treatment responses. Ultimately, BACTRAC has the potential to advance precision medicine approaches in stroke care by improving both prognostication and therapeutic development.
5. Looking ahead, what is your long-term vision for this work?
A recent priority identified by the National Institute of Neurological Disorders and Stroke (NINDS) is the development of the "neural exposome," which encompasses the cumulative physical, chemical, biological, social, and environmental factors that influence neurological health and disease. The BACTRAC framework closely aligns with this concept by integrating molecular data with detailed clinical and demographic information.
Our findings have demonstrated that local patient populations can exhibit distinct biological responses to stroke. This highlights the need for other institutions to establish similar thrombectomy-based biobanking programs and collaborate within a broader multi-institutional network. By creating regional and national neural exposomes, researchers can identify both shared and population-specific molecular pathways that influence stroke outcomes.
The long-term goal is to develop predictive models that accurately forecast functional and cognitive recovery while also identifying therapeutic targets tailored to individual patients. Such an approach would deepen our understanding of stroke biology and accelerate the transition toward truly personalized stroke care.