Weight drop models in rodents have been used for several decades to advance our understanding of the pathophysiology of traumatic brain injury (TBI). Creative Biolabs employs the Marmarou's weight-drop model (impact acceleration model) to evaluate potential preclinical therapies. This impact acceleration model using a weight-drop is a useful model for investigating diffuse brain injuries ranging from mild to severe.

Introduction of Weight Drop Model

The impact acceleration model of diffuse traumatic brain injury (DTBI), commonly referred as the Marmarou weight drop model, is widely utilized to replicate DTBI without focal lesion to characterize changes that closely parallel abnormalities characteristic of human DTBI caused by motor vehicle accidents or falls. This model involves head impact followed by prolonged loading into a foam pad under the animal. The device consists of a column of brass weights, which ultimately falls freely via gravity. The height from which they fall can be manipulated through a plexiglass tube.

Once the animal is anesthetized, a midline incision is made exposing the underlying skull. A stainless steel disc is then rigidly attached with cement to the skull in a central location between the bregma and lambda. The animals are then placed on a foam bed. The impact is generated by the free-falling weights falling directly onto the cemented stainless steel disc. It has been shown to reproduce neuronal and axonal pathology that is scattered throughout the cerebrum and brainstem. Depending on the severity of the injury, the induced brain injury results in hemorrhages, neuronal cell death, astrogliosis, diffuse axonal injury, and cytotoxic brain edema.

Rodent Weight Drop Model of Traumatic Brain Injury Fig.1 Cognitive function of mice with traumatic brain injury (TBI) using the passive avoidance test. (Khalin et al. 2016)

Features of Weight Drop Model

  • Weight drop animal models of TBI are relatively cheap to set up and easy to perform, and they show good replicability and well-studied neuropathology.
  • The severity of the injury can be manipulated based on changing pre-impact parameters such as varying the weights, the weight height, as well as post-impact implementation of secondary insults such as hypoxia and hypotension.

Assessments

To assess the injury severity level, there are multiple outcome measures that can be used (e.g., neurological, physiological, neurobehavioral, histological techniques). To measure the functional neurological and cognitive outcomes, a battery of behavioral tests can be conducted, such as beam walk test, Rotarod test, and Morris water maze. Non-behavioral parameters such as neuronal damage/loss can be measured with staining techniques. Magnetic resonance imaging analysis can be used to evaluate cortical lesion volume. Briefly, Creative Biolabs provides assessments including but not limited to:

  • Behavioral tests (e.g., motor function, cognition, social behavior)
  • Histology analysis (e.g., cortical lesion volume)
  • Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)

Additionally, we provide other TBI rodent models that you may be interested in:

The comprehensive list of rodent neurological disease models is placed below for your review. Please click the links for more detailed description of each model:

Creative Biolabs is more than just a CRO, we are a research partner that can help design the studies based on the goals at hand and thus all studies can be designed to maximize the amount of data that can be obtained from a single animal. For more information on our traumatic injury models please contact us or send us an inquiry below. If you are interested in developing new models of variations of already established models, contact us to discuss the possibilities and suggestions.

Reference

  1. Khalin, I.; et al. A mouse model of weight-drop closed head injury: emphasis on cognitive and neurological deficiency. Neural Regen Res. 2016,11(4):630-635.

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