Rodent models for studying spinal cord development and adaptive plasticity after injury
1 Formål: In this project we address major issues in the field of brain and spinal cord function and response to injury: how neuronal identities and synaptic connections are established, how adaptive plasticity after a spinal cord injury works at the molecular level, and whether adaptive plasticity can be manipulated at the molecular level to direct reorganization of synaptic connections and neuronal circuits after injury, and also to protect against the effects of injury. This project also stretches the boundaries of the medical implants by developing small devices that aim a replacing lost function in patients.
2 Skadevirkninger: Spinal cord injury inflicted at a young age (through P10) gives a temporary paralysis of the affected muscles with virtually complete functional recovery within 10 days. The young animals manage very well and cannot be distinguished from uninjured animals later. Spinal cord injury inflicted in older animals gives varying degrees of long-lasting paralysis, particularly in distal limb muscles. The animals exhibit some functional recovery and manage well. Animals are terminated if the injury results in obvious decrease in quality of life to the point that they cannot manage and thrive.
3 Forventet nytteverdi: Spinal cord injuries (SCI) impact significantly both the patient, their relatives, and society in general. SCI results in varying loss of connections between the brain and spinal circuits distal to the injury, with subsequent loss of muscular and autonomic function. Quality of life is greatly impaired, and the societal burden in the form of lost labor and rehabilitation costs are enormous. Today there is no effective therapeutic treatment. The novel insight from our animal studies will facilitate translational projects focused on repair, technological replacement, and recovery of function after SCI in humans. The project thus contributes to the development of new therapeutic avenues for clinical treatment of SCI.
4 Antall dyr og art: Maximum 900 mice/year (embryos, newborns, adults, both for breeding and for experiments) starting in 2024.
5 Hvordan etterleve 3R: The experiments are performed on the brain and spinal cord during prenatal and postnatal development and in adult mice. The brain and spinal cord are organs of immense complexity and it is currently not possible to replace these with computer models or in vitro cell cultures. We strive to keep the number of animals and experiments to the minimum that is compatible with the statistical strength required to guarantee reliable results. All animals that are operated, injured are analyzed by multiple methods (behavioral testing, electrophysiology, optogenetics, anatomical assays, immunohistochemistry etc.) to obtain the maximum amount of information from each animal.
With the new approach to genotyping soon after birth, we also expect to be able to diminish the number of animals that are not used for experiments (because of incorrect genotype) and simply discarded, and thereby minimize the total number of animals used in the project.
2 Skadevirkninger: Spinal cord injury inflicted at a young age (through P10) gives a temporary paralysis of the affected muscles with virtually complete functional recovery within 10 days. The young animals manage very well and cannot be distinguished from uninjured animals later. Spinal cord injury inflicted in older animals gives varying degrees of long-lasting paralysis, particularly in distal limb muscles. The animals exhibit some functional recovery and manage well. Animals are terminated if the injury results in obvious decrease in quality of life to the point that they cannot manage and thrive.
3 Forventet nytteverdi: Spinal cord injuries (SCI) impact significantly both the patient, their relatives, and society in general. SCI results in varying loss of connections between the brain and spinal circuits distal to the injury, with subsequent loss of muscular and autonomic function. Quality of life is greatly impaired, and the societal burden in the form of lost labor and rehabilitation costs are enormous. Today there is no effective therapeutic treatment. The novel insight from our animal studies will facilitate translational projects focused on repair, technological replacement, and recovery of function after SCI in humans. The project thus contributes to the development of new therapeutic avenues for clinical treatment of SCI.
4 Antall dyr og art: Maximum 900 mice/year (embryos, newborns, adults, both for breeding and for experiments) starting in 2024.
5 Hvordan etterleve 3R: The experiments are performed on the brain and spinal cord during prenatal and postnatal development and in adult mice. The brain and spinal cord are organs of immense complexity and it is currently not possible to replace these with computer models or in vitro cell cultures. We strive to keep the number of animals and experiments to the minimum that is compatible with the statistical strength required to guarantee reliable results. All animals that are operated, injured are analyzed by multiple methods (behavioral testing, electrophysiology, optogenetics, anatomical assays, immunohistochemistry etc.) to obtain the maximum amount of information from each animal.
With the new approach to genotyping soon after birth, we also expect to be able to diminish the number of animals that are not used for experiments (because of incorrect genotype) and simply discarded, and thereby minimize the total number of animals used in the project.