Protocol | Published:

Mouse closed head injury model induced by a weight-drop device

Nature Protocols volume 4, pages 13281337 (2009) | Download Citation

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Abstract

Traumatic brain injury represents the leading cause of death in young individuals. Various animal models have been developed to mimic human closed head injury (CHI). Widely used models induce head injury by lateral fluid percussion, a controlled cortical impact or impact acceleration. The presented model induces a CHI by a standardized weight-drop device inducing a focal blunt injury over an intact skull without pre-injury manipulations. The resulting impact triggers a profound neuroinflammatory response within the intrathecal compartment with high consistency and reproducibility, leading to neurological impairment and breakdown of the blood–brain barrier. In this protocol, we define standardized procedures for inducing CHI in mice and determine various severity grades of CHI through modulation of the weight falling height. In experienced hands, this CHI model can be carried out in as little as 30 s per animal, with additional time required for subsequent posttraumatic analysis and data collection.

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Acknowledgements

E.S. is the incumbent of the Dr Leon and Dr Mina Deutch Chair in Psychopharmacology (The Hebrew University of Jerusalem).

Author information

Affiliations

  1. Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, Colorado, USA.

    • Michael A Flierl
    • , Philip F Stahel
    • , Steven J Morgan
    •  & Wade R Smith
  2. Department of Neurosurgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, Colorado, USA.

    • Philip F Stahel
    •  & Kathryn M Beauchamp
  3. Department of Pharmacology, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.

    • Esther Shohami

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Contributions

E.S. originally developed this model. E.S. and P.F.S. modified the model further to the current version. M.A.F., P.F.S. and E.S. conceived and designed the study and wrote the paper. M.A.F., P.F.S. and K.M.B. conducted all experiments. S.J.M. and W.R.S. supervised the project and edited the manuscript.

Corresponding author

Correspondence to Michael A Flierl.

Supplementary information

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  1. 1.

    Supplementary Figure 1

    Specifications of the TBI apparatus. The device consists of three parallel horizontal plates [32.5 cm × 21 cm × 1.2 cm]. The upper and lower plates are made of metal, while the middle plate is made from Perspex. The surfaces are fixed by four metal bars (Ø 1 cm), that connect the plates (panel a). A metal rod weighing 333 g (length 82.5 cm, Ø 0.7 cm) that passes through the centre of the top and middle platforms, delivers the impact to the animal head which is fixed on a platform (9 cm × 9 cm) installed on the bottom plane (panels a, b). The flat silicone tip fixed at the end of the impacting rod has a diameter of 3 mm (panel b). An electric lock controlled by a foot touch switch allows a free fall until the silicone tip hits the animal's exposed skull. To allow for this locking mechanism, the falling rod is marked with several indentations (panel b).

  2. 2.

    Supplementary Figure 2

    Blueprints of the NSS equipment. All NSS devices are constructed from plastic. The exact measurements required for re-built of the “exit circle” device are depicted in panels a, b. The specification of the “beam walk” apparatus in the different planes is depicted in panels c, d and e, and the beam measurements are illustrated in panel f.

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https://doi.org/10.1038/nprot.2009.148

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