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The model NDI uses recognizes the rocky history of previous efforts to model traumatic injury to the brain. Instead of a single endpoint measure, multiple endpoints are used in a comprehensive study design, focusing on behavioral tests with clinical relevance.
Example of a specific study design
Animals: Mice or rats, 12 animals per group.
Behavior testing: Occurs at 4 time points (7, 12, 21, and 28 days post-lesion). Multiple time-point testing controls for post-lesion recovery in the absence of any treatment, allowing detection of an improvment in the rate of recovery by the test therapeutic.
Specific tests used:
- Von-Frey hairs on hind-paws (sensory-motor threshold)
- Inclined plane
- Forelimb flexion
- Forced lateral pulsion
- Rotorod
- Balance Beam walking
- Patterned walking
The reason for using multiple behavioral measures is to ensure that any positive behavioral effects of the test compound are not method-specific.
Histology
In many TBI studies, neuroprotection has been evaluated almost exlusively by measuring lesion size. It is now recognized that this measure is inadequate. A test therapeutic may reduce lesion size without having any effect on neuron survival. For this reason, we quantify any neuroprotection directly by counting neurons in the lesion area. In addition, a structure connected with the damaged cortical area (the hippocampus) is measured, to see if the test compound reduces the normal TBI-induced atrophhy of this structure. The importance of this measure is that hippocampus size is related to cognitive function.
Specific histological assays used:
- Measurement of hippocampus size
- Measurement of retrograde degeneration (NeuN labeling of neurons, which ar e counted directly)
- Measurement of lesion size
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