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A Mouse Controlled Cortical Impact Model of Traumatic Brain Injury for Studying Blood–Brain Barrier Dysfunctions

  • Himakarnika Alluri
  • Chinchusha Anasooya Shaji
  • Matthew L. Davis
  • Binu TharakanEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1717)

Abstract

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. It is a silently growing epidemic with multifaceted pathogenesis, and current standards of treatments aim to target only the symptoms of the primary injury, while there is a tremendous need to explore interventions that can halt the progression of the secondary injuries. The use of a reliable animal model to study and understand the various aspects the pathobiology of TBI is extremely important in therapeutic drug development against TBI-associated complications. The controlled cortical impact (CCI) model of TBI described here, uses a mechanical impactor to inflict a mechanical injury into the mouse brain. This method is a reliable and reproducible approach to inflict mild, moderate or severe injuries to the animal for studying TBI-associated blood–brain barrier (BBB) dysfunctions, neuronal injuries, brain edema, neurobehavioral changes, etc. The present method describes how the CCI model could be utilized for determining the BBB dysfunction and hyperpermeability associated with TBI. Blood–brain barrier disruption is a hallmark feature of the secondary injury that occur following TBI, frequently associated with leakage of fluid and proteins into the extravascular space leading to vasogenic edema and elevation of intracranial pressure. The method described here focuses on the development of a CCI-based mouse model of TBI followed by the evaluation of BBB integrity and permeability by intravital microscopy as well as Evans Blue extravasation assay.

Key words

Blood–brain barrier Controlled cortical impact Traumatic brain injury Intravital microscopy Evans Blue Edema Intracranial pressure Central nervous system Hyperpermeability Endothelial permeability 

Notes

Acknowledgments

The work presented in this chapter was supported by Scott & White Academic Operations Funds to Dr. Tharakan. The authors would like to apologize to investigators whose works are not cited in this methodological report due to space limitations and the personal perspective with which this chapter has been prepared.

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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Himakarnika Alluri
    • 1
  • Chinchusha Anasooya Shaji
    • 1
  • Matthew L. Davis
    • 1
  • Binu Tharakan
    • 2
    Email author
  1. 1.Department of Surgery, Texas A&M University Health Science Center, College of MedicineBaylor Scott and White Research InstituteTempleUSA
  2. 2.Department of SurgeryTexas A&M University Health Science Center, College of Medicine, Baylor Scott and White Research InstituteTempleUSA

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