Abstract

Current veterinary standards of biomedical research support include refinements in animal models that are targeted at enhancing humane care and decreasing inter-animal variability. This ultimately results in fewer numbers of animals being used and reduction in animal experimentation through mitigation of waste as well as faster research results. 6-hydroxydopamine-lesioning of the substantia nigra using a stereotactic frame device is a common procedure and is routinely performed under pentobarbital anaesthesia with monitoring by 8 h workforces. Our programme supports the humane care and use of several protocols involving the unilateral stereotactic-lesioning of rats for the purposes of creating research models of Parkinsonianism. Such procedures are commonly performed as unilateral in order to minimize aphagia and other untoward effects of the lesion. Generally, this procedure is considered minor because it involves a small incision, a cranial burrhole, and penetration of the dura. Inflammation and/or irritation of the ear canal can occur secondarily to the earbar placement procedure. Human patients undergoing similar procedures typically complain of headaches from loss of intracranial pressure; which is a transient outcome. Despite the perception of minor insult, we provided aggressive periprocedural care, and our veterinary staff documented weight loss that was often greater than 15% body weight during the first 3 days. The goal of this study was to evaluate refinements to improve this outcome. For humane concerns, and because of the need to begin experimental testing one week following surgery, a goal in the recent past has been to enhance outcome for researchers and animals by refining postoperative support modalities as well as by seeking the best anaesthetic regimen to shorten postoperative deviations from baseline. Analysis of three groups of rat patients lesioned by the same investigative group over the course of refinements made in our programme indicate that an early return of homeostasis was achieved by the use of inhalation anaesthetics as replacements for barbiturates in these models. Comparison with pentobarbital recipients also indicated that homeostasis is achieved earlier when barbiturates are utilized with fluid therapy and analgesics immediately after operative procedures rather than the next morning.

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