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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

Abstract

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.

Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

Introduction

Traumatic brain injury (TBI) accounts for more than two million hospital visits each year in the United States alone. Mild TBI commonly resulting from car accidents, sporting events, or falls represent approximately 80% of all TBI cases1. Mild TBI is considered the ‘silent disease’ as patients often experience no overt symptoms in the days and months following the initial insult, but can develop serious TBI-related complications later in life2. Moreover, blast-induced mild TBI is prevalent among military service-members, and has been associated with chronic CNS dysfunction3,....

Protocol

The protocol follows the animal care guidelines of the University of Cincinnati and West Virginia University. All procedures involving animals were approved by the Institutional Animal Care and Use Committees (IACUC), and were performed according to the principles of the Guide for the Care and Use of Laboratory Animals.

1. Installation of the blast TBI setup

  1. Acquire all the working parts that are required for the setup, including: shock tube consisting of steel dr.......

Representative Results

The scalability of the blast wave setup was tested using three different membrane thicknesses, 25.4, 50.8 and 76.2 μm. Peak pressure levels were assessed at the head placement area and the exit of the shock tube apparatus using piezoelectric pressure sensors (see Figure 1 & Figure 2). Peak pressures increase in concordance with membrane thickness at both sensor locations (Figure 3A,B), demonstrating that th.......

Discussion

We present here a preclinical mild TBI model that is cost-effective, easy to set up and execute, and allows for high-throughput, reliable, and reproducible experimental outcomes. This model provides protective shielding to peripheral organs to allow for focused investigation into mild TBI mechanisms while limiting the confounding variables of systemic injury. In contrast, other blast models are known to inflict damage to peripheral organs2,39,

Acknowledgements

We thank R. Gettens, N. St. Johns, P. Bennet and J. Robson for their contributions to the development of the TBI model. NARSAD Young Investigator Grants from the Brain & Behavior Research Foundation (F.P. and M.J.R.), a Research Grant from the Darrell K. Royal Research Fund for Alzheimer’s Disease (F.P.) and a PhRMA Foundation Award (M.J.R.) supported this research. This work was supported through pre-doctoral fellowships from the American Foundation for Pharmaceutical Education (A.F.L and B.P.L.).

....

Materials

NameCompanyCatalog NumberComments
3/8 SAE High Pressure Hydraulic HoseEaton AeroquipR2-6-6-36MAvailable from Grainger
3/8'' Quick Connect Female PlugsKarcherKAR 86410440
3/8'' Quick Connect Male PlugsKarcherKAR 86410440
ANY-maze video tracking softwareStoelting Co.ANY-maze software
Clear Mylar membraneePlastics.comPOLYCLR0.003http://www.eplastics.com/Plastic/Clear_Polyester_Film/POLYCLR0-003; Clear Mylar membrane is sold in various thicknesses. All are sold by vendor listed above.
Compound Slide Table (X2)Grizzly IndustrialG5757
Deadman Gas Control Ball ValveConeraco Inc.71-502-01"Apollo", Available from Grainger
Driver and driven section (murine)own design/productionn/aFor further information please contact the authors
Driver and driven section (rat)own design/productionn/aFor further information please contact the authors
Ear Muffs3M37274Available from Grainger
Gas Regulator - Hi Flow 3500-600-580Harris3003539
Helium GasAirGasHE 300Tanks are available in various sizes
Inhalation Anesthesia SystemVetEquip901806
Input ModuleNational InstrumentsNI 9223
IsofluraneBaxterNDC 10019-360-40Ordered by veterinarian
Laboratory Timer/StopwatchFisher Scientific50-550-352
Labview version 12.0National InstrumentsData Acquistion Software
Magnetic Dial Indicator/MicrometerGrizzly IndustrialG9849
MATLABMathWorksSoftware for pressure recording analysis
Oxygen RegulatorMedlineHCS8725M
PC for Data ProcessingDell
Polyvinylchloride Tubing - 25.4 mmFORMUFITP001FGP-WH-40x3
Pressure sensorsPCB Piezotronics102A05
Receiver USB ChassisNational InstrumentsDAQ-9171
Sensor Signal ConditionerPCB Piezotronics482C series
Stainless NSF-Rated Mounting TableGridmannGR06-WT2448
T Handle Allen Wrench - 3/16''S&K73310

References

  1. Bazarian, J. J., et al. Mild traumatic brain injury in the United States, 1998--2000. Brain Injury. 19 (2), 85-91 (2005).
  2. Meabon, J. S., et al. Repetitive blast exposure in mice and combat veterans....

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