BOX 5-1
Replacement, Refinement, and Reduction

Replacement

Methods to avoid or replace the use of animals in areas where they otherwise would have been used, including

•   using non-animal alternatives such as human volunteers, computer models, and in vitro techniques.

•   using animals of lower neurophysiologic sensitivities such as invertebrates.

Refinement

Improvement to scientific procedures and husbandry that minimize pain, suffering, distress, or lasting harm and/or improve animal welfare, including

•   improved procedures (e.g., surgery).

•   improved anesthesia.

•   improved housing and husbandry.

•   better welfare assessment.

Reduction

Methods that minimize the number of animals used (or maximizing information gained from a given number of animals), including

•   good environmental design and statistical analysis.

•   tissue sharing.

•   imaging.

SOURCES: Barnett presentation; Russell and Burch (1959).

is a complex event that begins within minutes of the mechanical injury and progressively worsens over the subsequent weeks to months.

Repair Strategies

After an injury, formation of glial scars inhibit central nervous system repair by creating both physical (e.g., cyst) and biochemical (e.g., inhibitory signals) barriers to axonal growth. The goal of any repair strategy is to fill any cysts, maintain glial/neuronal survival, limit scar formation, promote axonal regeneration, and make functional reconnections. Using animal models, researchers are studying injecting growth factors, blocking inhibitory signals (e.g., anti-Nogo [described by Lemon]), transplanting cells, bridging the gap using biodegradable scaffolds to align the axons, and promoting plasticity/sprouting of any remaining intact fibers. No one treatment alone is capable of repairing the spinal cord, Barnett noted. Current thought is that a combination of strategies will be required.



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