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4 Survival Studies
Pages 69-87

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From page 71...
... Electrolytic and radio frequency techniques, as well as those using neurotoxins, can be used to make brain lesions. Stereotaxic approaches are often used to make more focal lesions or lesions in deeper brain structures.
From page 72...
... Multiple Injections The scientific requirements of certain experiments may require subjecting a single animal to multiple injection procedures. As a result, when the injection site is a central brain structure, it will be necessary to subject an animal to multiple major survival surgeries.
From page 73...
... In both examples, the surgeries are "related components of a research project" (NRC, 1996) , and IACUCs may choose to grant approval for these multiple major survival surgeries.
From page 74...
... In the previous example, eye coils may be implanted to monitor eye position and microelectrodes may be placed in the brain to measure neural activity. Neurophysiology experiments on an awake, behaving animal frequently require that the animal be confined to a restricted working space for many reasons, such as to enable precise positioning of recording or stimulating electrodes into the correct region, to stabilize the spine or head for neurophysiologic recording, to maintain the animal's posture in relation to the behavioral task, to maintain the orientation of the animal relative to a sensory stimulus, to restrict the range of reach of an animal to prevent it from accidentally damaging implanted equipment that is exposed during recording sessions (e.g., electrodes or lead wires)
From page 75...
... Major surgery to implant hardware devices for head restraint, data collection, and stimulation can be accomplished with standard aseptic surgical techniques and typically can be performed in a facility dedicated to aseptic surgery (see Gardiner and Toth, 1999, and Lemon, 1984b, for discussions of surgical issues related to cranial implants)
From page 76...
... Additional animal welfare issues specific to or frequently encountered in neurophysiology experiments include head restraint systems, chairing nonhuman primates, multiple survival surgeries, modified surgical settings, asepsis during introduction of probes into the brain, monitoring the site surrounding implanted devices or hardware for signs of infection, dealing with rejected or failed implants, maintaining chambers free of infection, and periodic durotomy. Restraint During Neurophysiology Experiments in Awake, Behaving Animals Most experiments that involve the monitoring of neural activity require some limitation of the animal's working space and/or freedom of body movement (NIH, 1991~.
From page 77...
... Then, during a training or experimental session, the head-holder is attached to a freestanding platform to immobilize the head. Besides minimizing movement, these systems provide a structural element to which to anchor connectors from other surgically implanted monitoring devices, such as eye coil wires, chronically implanted recording electrodes, or indwelling cannulae for delivery of pharmacological agents.
From page 78...
... In this case, performing a second major survival surgery is necessary and justified to ensure that the eye coils will function reliably during the experimental session. Performing multiple major surgeries may also be the best surgical approach if doing so allows a major surgery to be performed in an aseptic surgical suite, rather than in a modified surgical setting.
From page 79...
... Procedures, such as treating surgical wounds as they heal, cleaning and maintaining implanted devices, and removing the granulation tissue that typically forms over the aura mater inside chronically implanted recording chambers (Lemon, 1984a; Toth and Gardiner, 1999) , are commonly performed under light anesthesia in a laboratory setting, using aseptic techniques within a local sterile field (NIH, 1991~.
From page 80...
... A microelectrode, micropipette, or microdialysis probe may then be implanted into the brain, maintaining asepsis in the area immediately around the site and using specialized equipment to position the device accurately. If the two-step approach is not feasible and if the laboratory can be sanitized and prepared to allow aseptic technique, the entire procedure may be performed as a single survival procedure in the laboratory (for more discussion of this subject see "Surgery and Procedures" in Chapter 31.
From page 81...
... Training laboratory personnel in identifying adverse reactions and fostering a team approach that includes veterinarians and husbandry staff will help to ensure the well-being of animals used in these types of studies. Monitoring the Site Surrounding an Implanted Device Sites surrounding implanted devices or hardware, such as chambers, headrestraint devices, eye coils, nerve cuffs, electromyography (EMG)
From page 82...
... A team approach involving veterinary staff, caretakers, neuroscientists, and technicians is critical to the long-term success of experiments that use animals with chronic implants. Occupational Health and Safety It is prudent to reiterate that risks, such as exposure to B virus, are associated with working with awake, behaving nonhuman primates (see "Experimental Hazards" in Chapter 2~.
From page 83...
... High-field MRI, SPECT, and PET techniques can also be used to provide in vivo longitudinal evaluation of receptor binding and gene expression following gene therapy (Auricchio et al., 2003; Kasper et al., 2002~. Each of those techniques allows researchers to test hypotheses about the functions of different regions of the brain on the basis of functional composition or physiologic activity.
From page 84...
... Special Considerations of Animal Maintenance in the Imaging Environment Some of the features of imaging machines that make them powerful tools create an environment that may be inhospitable to routine maintenance of anesthesia and monitoring of animals. For instance, the strong magnetic field associated with an MRI machine may damage ferromagnetic components in monitoring devices or traditional ventilators (Chatham and Blackband, 2001; Kanal et al., 2002)
From page 85...
... Furthermore, the potential for exposure to radiation from the animal and its bodily excretions after injection of radioactive tracers may have to be evaluated and appropriate actions taken to minimize the associated human health risks. Other considerations include thorough disinfection of the equipment if it is also to be used with human subjects or
From page 86...
... The host cells will then express the foreign gene, changing the genetic profile of the host cells (NIH, 1995~. During ex vivo gene transfer, cells, such as fibroblasts, are removed from the body and genetically modified, often with the same methods used for in vivo gene therapy.
From page 87...
... That document identified which kinds of experiments involving recombinant DNA required institutional biosafety committee approval or notification. Some of the designated experiments include research involving transgenic rodents and the use of infectious DNA or RNA viruses.


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