# Natural History of Traumatic Microvascular Injury

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2021 · $178,218

## Abstract

PROJECT SUMMARY
TBI is a prevalent and devastating health issue worldwide. Despite extensive research in neuroprotective
therapies, and success in pre-clinical models, multiple clinical trials have failed to demonstrate efficacy, such
that there are still no targeted treatments available for TBI. TBI is a heterogenous disease, influenced by
mechanical forces, genetic factors, and secondary insults that compound the primary injury. A major limitation
hindering the development of TBI therapies is the lack of reliable biomarkers of specific injury mechanisms in
TBI. Substantial data point to traumatic microvascular injury (TMI) as a key component of TBI-associated
disability: pathological studies demonstrate that TMI is a nearly universal, albeit under-studied, endophenotype
of TBI and vascular dysfunction underlies many of the chronic neurological symptoms that complicate TBI
recovery. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular
health, TMI is an attractive target for therapeutic intervention after TBI.
The central hypothesis of this proposal is that traumatic microvascular injury is a prominent TBI
endophenotype that is predictive of patient outcome. The objectives of the proposed study are to: (1) describe
the natural history of TMI using neuroimaging, (2) develop diagnostic and prognostic miRNA biomarkers of
TMI, and (3) describe the correlation between the neuroimaging and miRNA biomarkers and clinical outcomes
after traumatic brain injury. In the context of this study, the candidate will train in clinical and translational
research methods with focused, individualized mentoring to support her transition to independently funded,
patient-oriented research. This proposal will leverage an ongoing prospective cohort study of individuals with
traumatic brain injury who undergo detailed demographic, clinical, neuroimaging, and neuropsychological
assessments from their acute injury through chronic recovery.
In addition to completing the proposed research, the applicant will engage in a rigorous training program of
didactic courses and mentoring by experts in neurotrauma, brain imaging, miRNAs, and vascular biology. She
will gain expertise in clinical study design and management, sequencing and molecular laboratory techniques,
and advanced statistical methodologies relevant to clinical research. The applicant's progress and attainment
of specific benchmarks in research and career development will be regularly reviewed by her mentors who
have extensive experience in training junior investigators and facilitating their transition to independent
research careers. Completion of the proposed study will be facilitated by an institutional environment that
prioritizes collaboration, and provides exemplary research and career support. Through the conduct of the
proposed study, the applicant will make significant contributions to the understanding of traumatic
microvascular injury and describe neuroimaging and m...

## Key facts

- **NIH application ID:** 10241437
- **Project number:** 5K23NS104239-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Danielle Kaye Sandsmark
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $178,218
- **Award type:** 5
- **Project period:** 2017-09-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241437

## Citation

> US National Institutes of Health, RePORTER application 10241437, Natural History of Traumatic Microvascular Injury (5K23NS104239-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241437. Licensed CC0.

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