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Related Concept Videos

Traumatic Brain Injury l: Introduction01:28

Traumatic Brain Injury l: Introduction

DefinitionTraumatic brain injury, or TBI, is a disturbance of normal brain function induced by an external mechanical force, such as a direct blow to the head or a penetrating injury. It can affect both brain structure and function, producing a wide range of clinical outcomes. TBI is a heterogeneous condition, meaning its effects may differ based on the type, location, and severity of the injury.Basis of ClassificationTBI is classified based on severity, injury mechanism, or pathophysiology. In...

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Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier
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Three-Dimensional Human Neurovascular Unit Modeling Reveals Cell-Specific Mechanisms of Traumatic Brain Injury.

Liam H Power1, Evan C Marcet1, Zihong Chen1

  • 1Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.

Journal of Functional Biomaterials
|December 24, 2025
PubMed
Summary

Controlled cortical impact in a 3D human neurovascular unit model caused cell death and disrupted the blood-brain barrier. Cell interactions revealed specific injury responses and vascular dysfunction after traumatic brain injury.

Keywords:
cellular responsesneurovascular unit dysfunctiontraumatic brain injury

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Area of Science:

  • Neuroscience
  • Biomaterials Science
  • Cell Biology

Background:

  • Traumatic brain injury (TBI) involves neurovascular unit (NVU) damage, potentially leading to neurodegenerative diseases.
  • The specific roles and interactions of human NVU cells after injury are not well understood.

Purpose of the Study:

  • To investigate cell-type-specific responses within the human NVU following controlled cortical impact (CCI).
  • To elucidate the mechanisms of blood-brain barrier (BBB) disruption and vascular dysfunction after TBI using a human-based model.

Main Methods:

  • Developed a 3D human NVU model utilizing silk-collagen scaffolds.
  • Applied controlled cortical impact (CCI) to the NVU model to simulate TBI.
  • Analyzed cell death pathways, cytokine release (IL-1β), endothelial junctional protein regulation, and inflammatory molecule expression.

Main Results:

  • CCI induced acute cell death in astrocytes, microglia, and endothelial cells, but not pericytes, independent of apoptosis or necroptosis.
  • Astrocytes and microglia were key sources of IL-1β; astrocytes destabilized VE-cadherin, pericytes stabilized barrier proteins, and microglia affected Claudin-5.
  • Soluble factors from injured cells disrupted endothelial junctional proteins (ZO-1, Occludin) and increased adhesion molecules (ICAM-1, VCAM-1).

Conclusions:

  • Defined distinct cell-type-specific injury responses within the human NVU after trauma.
  • Revealed how NVU cell crosstalk regulates vascular dysfunction and BBB breakdown following TBI.
  • Established a human-based 3D model for studying TBI pathophysiology and developing therapeutic strategies.