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Paris, March 31, 2008

Repairing a damaged brain using correctly-targeted reinnervation

Scientists in the Laboratoire de Neurobiologie des Processus Adaptatifs (CNRS/Université Pierre et Marie Curie) have shown that it is possible to repair an injured brain by creating a small number of new, specifically-targeted innervations, rather than a larger number of non-specific connections. Behavioral tests have demonstrated that such reinnervation can thus restore damaged cerebral functions. These results, already on-line, were published in the journal Brain on April 1st, 2008.

Brain injury in adults can cause irreparable, long-term physical and cognitive damage.  However, motor and spatial functions can be recovered if undamaged neurons are stimulated to create new innervation. This type of innervation develops spontaneously after a brain injury in very young children.  Researchers had previously shown – based on injury to the neuronal pathway linking the stem to the cerebellum(1) – it was possible to induce reinnervation in young adults similar to that observed in newborn infants.  This repair was rendered possible by treating the damaged cerebellum with a peptide(2) called Brain Derived Neurotrophic Factor (BDNF) which plays a role in the development and satisfactory functioning of this neuronal pathway.

In the present case, the researchers have extended the use of this model and showed that the terminals of new axons interact with the network of undamaged neuronal cells to restore their associated functions, such as synchronized movement and spatial orientation. These results demonstrate a correlation between an improvement in behavior and the degree of reinnervation in the cerebellum. Thus a small amount of correctly-targeted reinnervation makes it possible to recover fine functions such as motor and cognitive skills.

These results open promising new perspectives and make it possible to envisage using BDNF – already employed during clinical trials on the treatment of neurodegenerative conditions such as Parkinson's disease – to repair the human brain after a cerebral lesion.

Cerveau lese 1

© CNRS Photothèque / BAILLY Yannick (This image can be obtained (reference 2000N01866) from the CNRS photo library at: http://phototheque.cnrs.fr/)

Image 1 - Fluorescence of the "green fluorescent protein" expressed under the control of bovine prion protein regulatory sequences in a Purkinje cell of the gfp-prp transgenic mouse cerebellum.


Cerveau lese 2

© DIXON Kirsty (this image is available from the CNRS photo library at: phototheque@cnrs-bellevue.fr)

Image 2 – A new afference/connection (in red) which has formed contacts on a target Purkinje cell (in blue), permitting functional restoration.



































Notes:

1) This neuronal pathway is referred to as the cerebellum to Purkinje cell climbing fiber pathway and it is implicated in the coordination of movements.
2) A protein that is normally present in the brain and is involved in its development and functioning.

References:

BDNF increases homotypic olivocerebellar reinnervation and associated fine motor and cognitive skill
Melina L. Willson(1,2), Catriona McElnea(2), Jean Mariani(1,3), Ann M. Lohof(1) and Rachel M. Sherrard(1,4)
1) Université Pierre et Maris Curie-P6, UMR7102, Paris, F75005-France; CNRS, UMR7102, Paris, F75005-France
2) School of Veterinary and Biomedical Sciences, James Cook University, Australia
3) Assistance Publique, Hôpitaux de Paris, Hôpital Charles Foix, UEF, F-94200, Ivry sur Seine, France
4) Developmental Neuroplasticity Laboratory, School of Anatomy and Human Biology, University of Western Australia, Australia
Brain (2008), 1st April 2008.

Contact information:

Researcher :
Rachel Sherrard
T 01 44 27 32 27/06 76 04 40 80
rachel.sherrard@snv.jussieu.fr

Public Information Officers :
CNRS
Laetitia Louis
T 01 44 96 51 37
laetitia.louis@cnrs-dir.fr

UPMC
Véronique Raoult
T 01 44 27 73 88
veronique.raoult@upmc.fr


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