Approved on September 25, 1998 to use 3810 rats. "Because we expect a low percentage or our animals will die during surgery, we will request additional 100 animals."

Approved July 26, 2001 an additional 2,500 rats. "From our previous experience, we found that about 20% of the infected animals died before their scheduled sacrifice. We would like to ask for 500 additional animals for control experiments and to ensure that we generate enough experimental animals."

Rationale for Using Animals
The rat has been selected for these studies because an extensive knowledge base exits on the structure and function of the central nervous system of the rat. In addition, we have generated extensive preliminary data on neurodegeneration induced by inflammatory cytokines in the rat brain.

Lay Abstract:
Brain Inflammation may cause severe brain tissue injury. But the mechanism of such inflammation induced brain injury is not known.

Pain or Distress
Rats are infected with the trypanosoma parasite to serve as the model for this experiment. The parasite induces a disease similar to African Sleeping Sickness. The disease causes specific degeneration of nerve fibers and cells in the brain which results in significant weight loss and disrupted sleep.

Rats will be chronically infused with inflammatory cytokines intracerebrally viw implanted mini-pumps. The cytokines are thought to be mediators of neurodegenerative diseases such as African Sleeping Sickness. Infusion of high dose cytokines may even cause death.

The animals are expected to get sick and sick animals will not be euthanized prior to the completion of a study. Dead animals will be removed as soon as they are found, and cages will be checked regularly. In addition, we cannot accurately predict which animals will die due to our treatment. Our experience has shown that some treated animals which appear 'close to death' may recover and others may die without overt symptoms of sickness. Therefore, we will not remove animals which appear sick physically.

However, the following criteria will be used for the early removal of animals: 1) self-mutilation, 2) uncontrolled, violent motor behavior, 3) spontaneous vocalization, and 4) discharge at the site of surgery. These animals will be euthanized when they are found.