Neuroprotection and electrical stimulations to restore movements after spinal cord injury
1 Formål
Although very important for research, small animal models for spinal cord injury (SCI), such as mice and rats, have disadvantages. As a result, experimental treatments that have been successful in these models have failed to translate into clinical use in humans. In the past years, we have developed a pig model for SCI with the objective to obtain a relevant animal model for testing new experimental treatments that could further translate to clinic. We have built a team of experts within different specialties, such as veterinary medicine, neurosurgery, neuroscience, rehabilitation and functional electrical stimulation. All procedures have been established before and we would now like to focus our efforts towards testing new experimental therapies, such as neuroprotection, electrical stimulation, re-myelination, replacement of function using new technologies etc. The model was originally developed in Norway in a collaboration between Oslo university Hospital and the Faculty of Veterinary Medicine at the Norwegian university of Life Science during acute experiments (FOTS ID 7089). In addition, we acquired experience in the chronic phase (14 weeks post-operative), in collaboration with the Biomedical Research Foundation Academy of Athens. Based on that, we now propose to perform a new series of experiments that will bring us closer to a treatment for human SCI.
2 Skadevirkninger
An injury of the spinal cord will be created while the animals are under general anesthesia. We estimate the severity level of these experiments to be severe (betydelig). The injury produced and the placement of stimulation electrodes and pulse generators are invasive and creates intraoperative nociception and postoperative pain. Of note, surgical placement of electrodes and pulse generators is currently clinical practise in human patients for different applications. However, the surgical procedure will be done under deep anesthesia and the post-operative management involves pain treatment and care to reduce suffering and stress. The treatments we want to test require some spared spinal tissue and spared function. Hence, the injury created is per definition incomplete (Fig. 1G). This is a substantial advantage for the post-operative management and welfare of the minipigs. The treatments are based on (1) rescuing the tissue after injury and (2) strengthening the spared networks with electrical stimulation of the relevant neural circuits. This will require implantation of electronic devices. Some of them are already certified for human use and others are experimental. When used appropriately they are known not to create adverse effects.
3 Forventet nytteverdi
The benefits for patients and society could be invaluable. For the patients, even a small additional recovery is a great achievement and it will result in increased independence and life quality. For society, it could result in reduced health care costs, launch of new start-ups and an increased visibility of Norwegian research internationally.
4 Antall dyr og art
To obtain meaningful data, we calculated that we need 30 minipigs over a time course of 4 years.
5 Hvordan etterleve 3R
Replacement of animal experiments in this research area is unfortunately not possible, however, refinement and reduction is addressed in this application.
Although very important for research, small animal models for spinal cord injury (SCI), such as mice and rats, have disadvantages. As a result, experimental treatments that have been successful in these models have failed to translate into clinical use in humans. In the past years, we have developed a pig model for SCI with the objective to obtain a relevant animal model for testing new experimental treatments that could further translate to clinic. We have built a team of experts within different specialties, such as veterinary medicine, neurosurgery, neuroscience, rehabilitation and functional electrical stimulation. All procedures have been established before and we would now like to focus our efforts towards testing new experimental therapies, such as neuroprotection, electrical stimulation, re-myelination, replacement of function using new technologies etc. The model was originally developed in Norway in a collaboration between Oslo university Hospital and the Faculty of Veterinary Medicine at the Norwegian university of Life Science during acute experiments (FOTS ID 7089). In addition, we acquired experience in the chronic phase (14 weeks post-operative), in collaboration with the Biomedical Research Foundation Academy of Athens. Based on that, we now propose to perform a new series of experiments that will bring us closer to a treatment for human SCI.
2 Skadevirkninger
An injury of the spinal cord will be created while the animals are under general anesthesia. We estimate the severity level of these experiments to be severe (betydelig). The injury produced and the placement of stimulation electrodes and pulse generators are invasive and creates intraoperative nociception and postoperative pain. Of note, surgical placement of electrodes and pulse generators is currently clinical practise in human patients for different applications. However, the surgical procedure will be done under deep anesthesia and the post-operative management involves pain treatment and care to reduce suffering and stress. The treatments we want to test require some spared spinal tissue and spared function. Hence, the injury created is per definition incomplete (Fig. 1G). This is a substantial advantage for the post-operative management and welfare of the minipigs. The treatments are based on (1) rescuing the tissue after injury and (2) strengthening the spared networks with electrical stimulation of the relevant neural circuits. This will require implantation of electronic devices. Some of them are already certified for human use and others are experimental. When used appropriately they are known not to create adverse effects.
3 Forventet nytteverdi
The benefits for patients and society could be invaluable. For the patients, even a small additional recovery is a great achievement and it will result in increased independence and life quality. For society, it could result in reduced health care costs, launch of new start-ups and an increased visibility of Norwegian research internationally.
4 Antall dyr og art
To obtain meaningful data, we calculated that we need 30 minipigs over a time course of 4 years.
5 Hvordan etterleve 3R
Replacement of animal experiments in this research area is unfortunately not possible, however, refinement and reduction is addressed in this application.