Forsøksdyr: Plasticity and ependymal cell response to spinal cord injury (continuation/completion of 18042)

Godkjenningsdato 08.07.2020

Godkjenningsperiode 03.08.2020-03.08.2022

1. Purpose:
In this study we wish to track the proliferation and migration of adult neurogenic niche-derived and mature neural cells and in response to artificially induced traumatic brain and spinal cord injury in Sprague Dawley rats.

2. Expected injury (Moderate):
SCI: The animals will get a small surgical wound on the back at from T8-T12 that will be used to perform a T10 laminectomy of the spinal column. The spinal cord will be lesioned by applied pressure. This will result in partial/complete paralysis of the animal's body posterior to the lesion site.
TBI: The animals will receive a small surgical wound to the head, along with 2 bilateral craniectomies. Through these a clipped cannulae will be lowered to lesion the brain at either the Subventricular or Subgranular zones (neurogenic niches). Lesions will be on par with injection wounds and electrode implantations, resulting in minimal averse effects for the animals lesioned.

3. Expected gains:
Our study aims to uncover the cellular and molecular mechanisms by which the adult neurogenic niches respond to traumatic injury, and how to best mimick these conditions in vitro. This will enable us to identify potential processes that can be targeted therapeutically early on after injury, promoting a faster and/or more efficient healing process and significantly reduce the strain on animals involved in this kind of research. We also aim to improve the way in which mature neural cells are harvested from adult animals, both to study the beforementioned phenomena, but to reduce the overall need for animals to study neuronal function in vitro.

4. Number of animals.
For this study we desire the use of 70 animals (40 from original application, 30 additional from this application) based on a previously completed pilot and study and in vitro work using these procedures (FOTS ID: 16066/18042).

5. 3R's:
Replacement - Animals cannot be replaced in this study as no sufficient replacement model yet exists (this work aims to improve this).
Reduction - Stem cell samples will be harvested from a subset of the animals to test all aspects of adult neurpgenic niche proliferation and characteristics possible in vitro. This will reduce the load of work required in vivo and thus the amount of animals needed. However, some of these aspects requires testing in vivo, and a pilot study (FOTS ID: 16066) and the first part of this study has been performed and significantly optimized surgical/harvest/culturing procedures, resulting in a significant reduction in animals needed with a higher yield of data on a per-animal basis.
Refinement - A pilot study and in vitro work has been performed to optimize experimental procedure to ensure a appropriate number of animals will be used to achieve significant results without unnecessary waste as well as making us aware of any issues that might arise, so they can be better dealt with in regards to the welfare of the animals. Pain relief will be administered proactively throughout the duration of the study to ensure minimal stress and discomfort for the animals.

Ongoing research work in our group focuses in the development of advanced modelling platforms, which enable us to study aspects of spinal cord injury pathology in vitro, directly contributing to all 3R principles in this study.