Disease Models

Traumatic Brain Injury: What Maze Studies can Teach Us about It

By July 7, 2015 No Comments

Picture this: a good friend of yours just got out of a nasty car accident and you go to visit him in the hospital. The first thing you notice is that his attitude’s taken a nosedive, and he can hardly remember who you are. You stand there shocked and upset, but not surprised at all.

The scenario above is an example of the effects of Traumatic Brain Injury (TBI). As you can guess, TBI results from sustaining a nasty and powerful blow to the head, usually from one of the following:

  • Car accidents (as above)
  • Contact sports (i.e., boxing, football, rugby, etc…) or
  • Simply bumping your head roughly against a hard surface

This commonality has led to affect millions worldwide, and the subsequent effects make it all the worse. These include:

  • Memory impairments
  • Personality changes
  • Impairments to movement and other neurocognitive deficits

Animal studies and clinical trials have served as the mainstay of TBI research, largely because of the controlled environment they present. In today’s edition of the Maze Engineers blog we’re going to be looking at the differences that sex differences play in these studies, as well as methods and materials used, and uses and therapies that can be derived from them.

Mazes

The mazes used in this study were the Open Field (OF), Rotarod, Y-Maze, and the Morris Water Maze (MWM).

Here is a list of each mazes’ features, as well as when they were used during testing:

OF (Days 1, 7, 14, 21):

  • Used to study general motor activity
  • Can be rectangular or circular in construction
  • Walled to prevent escape
  • Marked with grids to better assess location
  • Rodent activity is recorded with overhead cameras and infrared beams
  • Rodent activity and anxiety is assessed via rearing and amount of time spent moving

Rotarod (Days 1, 2, 3, 7, 14, 21):

  • Built with an overhead rotating rod above several segments
  • Subjects apply force onto the rod by moving on it while avoiding falling to the ground
  • Balance, motor coordination, and grip are assessed here
  • This makes it very effective when assessing the effects of TBI and experimental drugs

Y-Maze (Day 10):

  • Used to study working memory
  • Built with three arms situated at 120o angles
  • Visual cues are placed at certain parts of the maze arms
  • Built with an open roof to allow other objects in the room to serve as visual cues
  • Overhead cameras were installed to record activity

Morris Water Maze (Days 23-26):

  • Used to study spatial learning and memory
  • Circular tank filled with water, with a transparent platform placed in the middle
  • Several starting points were placed along the maze, with the subjects tasked with finding the platform from each point

Pathological Models

Prior to the study a group of mice were subjected to a procedure called controlled cortical impact (CCI), an experimental brain injury method that uses a pneumatic mechanism to deliver trauma to the subject’s head.

Histological Assessments

After testing, the mice were euthanized and had their brains preserved for analysis. Eight brains (both male and female) were randomly selected for lesion analysis. For this, the lesioned sections were placed on slides, stained with cresyl violet, and scanned.

The variables analyzed for effect of injury were sex, injury (no CCI, mild CCI, or severe CCI), and which maze they were tested on (Water maze, rotarod, etc…). Two other measures (lesion volume analysis and tests performed only once) were evaluated across injury and sex. Therefore, the two most important variables of this study were sex and injury.

To measure the lesions the damaged volume was the focus of attention, and was calculated as the area of the opposite hemisphere minus that of the target hemisphere, multiplied by 0.54 mm.

Results and Potential Treatments

The study found that:

  • CCI exhibited the same effects across both sexes
  • Females mice exhibited more movement than did males
  • Mice with TBI are more active than those without
  • Severe TBI leads to higher anxiety in both male and female mice
  • TBI impairs motor activity and coordination, as well as working memory
  • Female mice with TBI swim faster than males, but perform equally overall

As well as the theoretical aspect of this study, it’s important to consider the possible benefits and treatments found here. One of the chief findings of this study is that drugs’ adverse effects are more severe for women. Thus, it would be wise for physicians and caretakers to devise more effective treatment and rehabilitation methods based on these findings. This would include:

  • Designing more effective drugs that target specific symptoms of TBI (motor impairments, mood, etc..)
  • Designing and improve tools to assess motor, memory, and other impairments

There have already been a number of studies based off of these findings, and have investigated:

  • The use of CDP-Choline on MWM performance
  • Whether single or mixed medications are more effective in TBI treatment
  • Utilizing craniectomy as an alternative to drug-based medication

Reference

Tucker LT, Fu AH, & McCabe JT (2015). Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. Journal of neurotrauma PMID: 25951234

About Tim Maze