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Preclinical contract research: animal models of neurological disorders:

Preclinical Traumatic Brain Injury Models (TBI models)

     Drugs designed to act at a single receptor site in the brain often fail clinically because of the complex nature of traumatic brain injury.  The TBI efficacy model offered by NeuroDetective is designed to be responsive to test therapies with multiple potential targets and mechanisms of action, over a protracted recovery period.

 

         Example study design

     Forty-eight adult male rats are used, plus six rats for backup in case of loss during surgical procedures.  These are divided into four groups (n = 12) as follows:

Group 1   Lesion plus Vehicle

Group 2   Lesion plus one dose of test compound

Group 3   Sham lesion plus Vehicle

Group 4   Sham lesion plus same dose of test compound

 

     Group identity is blinded to the investigator to reduce experimental bias.  The animals are given the agent or vehicle injections IP or SC beginning immediately after controlled cortical impact injury.  All animals are examined on a series of behavioral tests (tabulated below) which have been shown to be sensitive to the type of injury inflicted.  Upon completion of behavioral testing, brains are harvested and cut on a cryostat for examination of lesion reconstruction and hippocampal atrophy, and for measurement of retrograde degeneration (NeuN stain for counting neurons).

 

  MEASURES OUTCOMES & ANALYSIS DAYS / NUMBER OF TESTS
1

 SENSORY NEGLECT

Tactile adhesive removal

Latencies to remove the stimuli from their front paws with their mouths  One day pre-surgery and 3, 7, 14, and 21 days post-injury 
2

 MOTOR COORDINATION

accelerating rotorod

Latency to fall off a rotorod  One day pre-surgery following training (baseline) 3, 7, 14, and 21 days post-injury 
3  SPONTANEOUS LOCOMOTOR ACTIVITY

Number of vertical movements

Time spent in the center of box

Time spent in the corners 

Total horizontal distance traversed 

1, 3, 7, 14 and 21 days post-injury 
4

 MEMORY / COGNITION

Morris water maze

Latency to the platform

Length of the path to the platform

Exploration pattern: % total time spent in the outer vs. inner annuli

Probe trial: Time spent in the quadrant that previously contained the platform as a % of total time spent in the pool 

Daily beginning 10 days post-injury for 10 days, 4 trials each session

Probe trial given on 11th day of testing 

5  HISTOLOGY

Measurement of hippocampal atrophy

Measurement of retrograde degeneration (Neun labeling for counting neurons)

Measurement of necrotic cavity 

Post-surgery 21 days 

  

For a published example study (Click here) 

 

 
 

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