Our group is investigating the molecular mechanisms responsible for the decreased capacity of the adult central nervous system (CNS) to regenerate after an injury such as spinal cord injury, brain trauma or stroke. After spinal cord injury, nerve fibres of the spinal cord are typically disrupted and new outgrowth is very limited.

The top figure shows a section through a rat spinal cord after spinal cord injury. A scar has formed at the site of the lesion and disrupted nerve fibres have been stained (black). The bottom figure is a MRI of a human subject after spinal cord injury. The white box indicates the site of the injury, where a vertebra has damaged the spinal cord (black region in the spinal cord).

The search for cellular and molecular differences between the peripheral nervous system (PNS), which allows for regeneration, and the CNS has lead to the characterization of a protein inhibiting nerve outgrowth which we called "Nogo-A". 

In the meantime we could show that Nogo-A is mainly located in oligodendrocytes which are the cells ensheathing the nerve fibres of the CNS by a structure called myelin, thereby enhancing the conductance of nerve signals. In addition, Nogo-A has an important function as a ‘stop signal’ for outgrowing adult CNS nerve fibres. Further investigation of the molecular mechanisms involved in these processes is ongoing.

To show that Nogo-A has a significant function in vivo, we use different animal models to study regeneration. For example, hand tame rats which are partially lesioned in the spinal cord are treated with an antibody against Nogo-A or with a control antibody for two weeks starting immediately after the injury. The recovery of the animals is observed over weeks with behavioural tests such as walking on beams and ladders or the swimming test shown below.

Anatomical analysis of the spinal cord of these animals reveals that different regeneration processes take place: A) Regenerative sprouting caudal to the lesion site (white area), B) fibre outgrowth over tissue bridges, and C) sprouting of intact fibres.

The long range goal of this research is to contribute to the development of a treatment of CNS injuries such as spinal cord injury. For detailed information on our latest research please refer to the publication list.