# Platelets and Microvascular Dysfunction in Traumatic Brain Injury

> **NIH VA IK2** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2024 · —

## Abstract

Platelets are increasingly recognized to be essential mediators of inflammation, independent of their role in
thrombosis and hemostasis. Platelet recruitment to microvascular endothelium is a critical initial step in the
inflammatory response. Although platelets have been shown to contribute to vascular dysfunction in the acute
phase of traumatic brain injury (TBI), the role platelets play in persistent TBI symptomology is incompletely
understood. TBI affects a large portion of Veterans, and Veterans who experienced TBI are at increased risk for
chronic neurological impairment with great detriment to quality of life. Currently, there is a distinct lack of effective
therapeutics aimed at preventing these long-term TBI complications. The mechanisms by which acute injury
transitions to persistent symptomology are not well understood. To address this knowledge gap, the proposed
studies will use an innovative strategy combining real-time high-resolution intravital microscopy and a controlled
cortical impact (CCI) model of injury in a repeated-measures study of TBI.
The CCI model is a well-established models for replicating the neuronal cell death and overt vascular breakdown
which results from TBI and highlights the diffuse systemic coagulation which can result from brain injury. TBI
results in platelet activation and an acute disruption in the blood brain barrier (BBB) which may predispose
individuals to the development of long-term complications including neurodegenerative disorders. Despite this,
very little research has been conducted investigating the platelet-dependent changes that occur during the
transition from the acute phase of TBI to the chronic phase of injury. The mentor's laboratory has significant
expertise with platelet-microvessel interactions in systemic vascular beds and various models of inflammation.
The applicant recently developed a chronic cranial window model of repeated-measures imaging of the cortical
vasculature combined with a CCI model of TBI. Preliminary data generated in this model provide evidence of
pathological platelet-microvessel interaction and platelet extravasation into cortical tissue, concomitant with
disruption of the BBB, in the uninjured cortex contralateral to the site of injury. We will use this novel
approach to examine the longitudinal profile of platelet-endothelial interaction and BBB disruption that occurs
over the development of chronic TBI. The overall objective of this application is to determine the contribution of
platelets to the longitudinal cerebrovascular changes following TBI, and to determine the molecular mechanisms
responsible for platelet-microvessel interactions and cerebrovascular dysfunction following TBI. Our central
hypothesis is that platelet-microvessel interaction contributes to the cerebrovascular dysfunction, BBB
disruption and functional deficits found in the acute and chronic phases of TBI. This hypothesis was
formed based on the current literature in conjunction with our o...

## Key facts

- **NIH application ID:** 10923658
- **Project number:** 1IK2BX006462-01A1
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** Justin A Courson
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923658

## Citation

> US National Institutes of Health, RePORTER application 10923658, Platelets and Microvascular Dysfunction in Traumatic Brain Injury (1IK2BX006462-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10923658. Licensed CC0.

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