• strict warning: Only variables should be passed by reference in /info/wwv/data/uni/kar/sites/all/modules/inline/inline_upload.module on line 325.
  • strict warning: Only variables should be passed by reference in /info/wwv/data/uni/kar/sites/all/modules/inline/inline_upload.module on line 325.
  • strict warning: Only variables should be passed by reference in /info/wwv/data/uni/kar/sites/all/modules/inline/inline_upload.module on line 325.
  • warning: Creating default object from empty value in /info/wwv/data/uni/kar/includes/common.inc(1695) : eval()'d code on line 10.

A difficult nut to crack - regeneration in the central nervous system

At first sight the fields of work of Tübingen neurosurgeons could not be more varied. The scientists at the University Hospital in Tübingen are working on the regeneration of the auditory nerve and on the restoration of bladder function. The thing that this has in common is that the regeneration of function requires nerve fibres to grow back and restore lost functions.

Once the nerve system in humans is fully developed, there are genetically determined mechanisms that prevent further neural growth. However, if a peripheral nerve is damaged, nerve fibres can grow back spontaneously – at least to a certain extent. The regeneration of nerve fibres depends on the availability of growth promoting factors that are provided by the Schwann’s cells and the myelin sheath it produces.

After central nervous system (CNS) damage, the nerve fibres also try to grow back. They form small protuberances that nevertheless grow no more than a few millimetres. The reason for this is that, in contrast to myelin of the peripheral nervous system (PNS), myelin of the CNS contains factors that inhibit nerve growth. Prof. Martin Schwab from the ETH Zurich already found in the 1980s that the myelin sheath of the CNS has a negative effect on regeneration. Nowadays several inhibiting proteins (e.g., NOGO-A) are known.

Release the growth brake

Researchers at the Hospital of Neurosurgery at the UKT are investigating such inhibitory proteins in order to enhance nerve growth following damage. The team led by Prof. Dr. Marcos Tatagiba, Medical Doctor of the Hospital of Neurosurgery, has found a way to block growth-inhibiting proteins using specific antibodies and thus enable a therapeutically effective regeneration of the nerves.

Schematic presentation of the auditory pathway. (Figure: UKT/Hospital of Neurosurgery)

Schematic presentation of the auditory pathway. (Figure: UKT/Hospital of Neurosurgery)

Tatagiba is currently investigating this effect on rats that have lost the ability to hear because of a cut lesion. "If we apply the rat antibodies against NOGO-A we can observe fibres that grow beyond the lesion. This is a morphological sign that something is happening. In addition, electrophysiological recordings reveal typical nerve signals behind the lesion. We interpret these signs as regeneration but behavioural experiments show that the rats have not regained hearing," said Tatagiba.

Morphological examination of the central and peripheral auditory pathway (HE staining) (Figure: UKT/Hospital of Neurosurgery)

Morphological examination of the central and peripheral auditory pathway (HE staining) (Figure: UKT/Hospital of Neurosurgery)

Tatagiba is now hoping to clarify this contradiction. In the framework of a three-year STERN BioRegion BioProfile project, Tatagiba hopes to shed light on the matter by working in cooperation with scientists from the ENT Hospital. Initially, the researchers are investigating whether the regenerating fibres are able to form synapses. They will also try to find out whether it is possible to keep the neurones of the spiral ganglion alive. The cells in this nerve ganglion in the inner ear normally die almost totally when the auditory nerve is cut through. It is presumed that an interruption prevents the transport of neurotrophic factors which are vital for the cells of the spiral ganglion.

The researchers hope that the results are the first step towards successful treatment of deafness. If deafness is due to auditory nerve damage or due to tumours like acoustic neurinomas, then it might one day be possible to restore hearing using antibodies that block nerve growth inhibitors.

Comparison between surface and penetrating electrodes with regard to the tonotopy in the hearing centre of the brain stem (Figure: UKT/Hospital of Neurosurgery)

Comparison between surface and penetrating electrodes with regard to the tonotopy in the hearing centre of the brain stem (Figure: UKT/Hospital of Neurosurgery)

Regeneration of hearing with implants

Acoustic brainstem implants (ABIs) represent a completely different approach to hearing regeneration. Different types of ABI implants are available for the treatment of hearing impairment. Implants in the form of surface electrodes are placed directly above the core of the auditory nerve (nucleus cochlearis) in the brainstem. In cooperation with their partners from the NMI Natural and Medical Sciences Institute in Reutlingen, the neurosurgeons from Tübingen are working on alternatives because they feel that penetrating electrodes have a much better effect.

The biggest obstacle is the biocompatibility of the electrodes which need to have a suitable surface that prevents damaging interaction with body cells and fluids. That is why the project partners are testing different materials and biological coatings. The electrodes must also be sufficiently flexible. "The brainstem pulsates with the heartbeat. That’s why we need electrodes that are stiff enough to securely attach them to the site required. On the other hand, these electrodes need to become flexible at room temperature so that they do not cause any injuries," said Tatagiba.

The regeneration of nerves enables bladder control even in cases of paralysis

This clinically oriented project investigates the possibility of regenerating bladder function in paralytic patients, and it involves the transplantation of nerves. The surgeons combine two peripheral nerves with each other, where the reflex bow in the spinal marrow is located high enough to prevent the lesion above effecting the transmission of signals. "We connect the motor root, which is important for leg movement, with the nerve that controls bladder contraction," said Tatagiba explaining the simple concept. The patients can then move their hands over a specific part of the femur, which induces the bladder to empty. This project is carried out in close cooperation with urologists of the University Hospital in Tübingen.

The method works well – at least in principle. The scientists are now working on the optimisation of the method. They are investigating whether the nerve root of one half of the body is better suited than the other or whether it is necessary to transplant on both sides for best results. Should the scientists succeed in successfully connecting two peripheral nerves, then it is not a big step to using the CNS as a kind of bridge. As soon as Tatagiba and his team have enough money, they will look into the fascinating option of nerve regeneration in greater depth. Despite his optimism, Tatagiba also understands the limits of this approach and does not want to raise false hopes: "The spinal marrow function is highly complex. That is the reason why complete regeneration is highly improbable." However, the regeneration already foreseen will undoubtedly lead to an improvement in body function and hence quality of life.

leh - 17.10.2006
© BIOPRO Baden-Württemberg GmbH, first published at www.bio-pro.de<, the Biotech/Life Sciences Portal of the State of Baden-Württemberg. All rights reserved.

Further information:

University Hospital of Tübingen
Hospital of Neurosurgery

Prof. Dr. med. Marcos Tatagiba
(Medical Director)
Hoppe-Seyler-Straße 3
72076 Tübingen

Phone: +49 (0)7071 29-80325 (Secretarial Offices)
Fax: +49 (0)7071 29-4549
marcos [dot] tatagiba [at] med [dot] uni-tuebingen [dot] de
www.medizin.uni-tuebingen.de/neurochir<