Mechanisms of axonal growth in plasticity and regeneration

• Research unit: EU RFP
• Project number: 96.0049

Key words (English)

Spinal cord; brain; injury; regeneration; plasticity; sprouting; functional restoration

Alternative project number (English)

EU project number: BIO4CT960774

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Short description (English)

See abstract

Partners and International Organizations (English)

M. Bähr (Tübingen) (Koordinator), E. Arenas (Stockholm), L. Maffei (Pisa), C. Sotelo (Paris), P. Strata, (Turin)

Abstract (English)

In the mature central nervous system (CNS) compensatory growth of surviving fibers or regeneration of lesioned fibers is normally not seen after injury. This lack of fiber growth is correlated with the myelination of the system and is, for a large part, due to the presence of growth inhibiting molecules. One of these molecules, that is expressed by oligodendrocytes, is Nogo-A formerly known as NI-35/250. This molecule has now been purified and characterised and the nogo gene has been found to encode for 3 major alternative splice products (Chen et al.). A monoclonal antibody (mAb IN-1) as well as a recombinant Fab fragment have been raised against the inhibitory protein. These neutralising agents are applied in different in vivo paradigms to evaluate the mechanisms of axonal growth after CNS injury.

Adult rats treated with either mAb IN-1 or IN-1 Fab fragment after spinal cord injury showed long-distance regeneration of corticospinal axons and these fibers formed terminal varicosities in the grey matter of the spinal cord (Brösamle et al.). The locomotor capacity and the locomotor control of these rats were assessed during the rehabilitation phase using a number of well established tests (BBB-score, kinematic analysis, gridwalk, narrow beam). Changes in the locomotor pattern were visualised with electromyographic (EMG) recordings. Nociception was evaluated at the beginning and at the end of the experiment using the tail flick test. Improved recovery of the IN-1 treated animals was seen consistently in all behavioural tests as well as in the kinematic analysis compared to control treated rats. No differences between the groups were seen in the tail flick test, indicating that IN-1 treatment did not affect nociception. Anatomical evaluation revealed regeneration of lesioned corticospinal tract (CST) fibers as well as sprouting of spared axons. CST and rubrospinal tract (RST) are the two most important tracts for voluntary muscle control in the rat. The response of the rubrospinal tract in adult rats has now been studied after a bilateral lesion of the CST at brain stem level (pyramidotomy). In the presence of antibodies to the neurite growth inhibitor Nogo-A RST fibers sprout and invade target zones of the CST in the ventral horn of the spinal cord. This observation supports the concept that major spinal tract systems can reorganise after injury in the adult animal if growth inhibitory factors are suppressed experimentally.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 96.0049