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Damaged Brain Can Be Repaired, Study Suggests

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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.

A new afference/connection (in red) which has formed contacts on a target Purkinje cell (in blue), permitting functional restoration. (Credit: Copyright Dixon Kirsty)
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.

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.

Brain. 2008 Apr;131(Pt 4):1099-112. Epub 2008 Feb 25.
BDNF increases homotypic olivocerebellar reinnervation and associated fine motor and cognitive skill.
Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 7102-Neurobiologie des Processus Adaptatifs (NPA), Centre National de la Recherche Scientifique (CNRS), UMR 7102-NPA, F-75005 Paris, France.

Recovery of complex neural function after injury to the adult CNS is limited by minimal spontaneous axonal regeneration and/or sprouting from remaining pathways. In contrast, the developing CNS displays spontaneous reorganization following lesion, in which uninjured axons can develop new projections to appropriate target neurons and provide partial recovery of complex behaviours. Similar pathways can be induced in the mature CNS, providing models to optimize post-injury recovery of complex neural functions. After unilateral transection of a developing olivocerebellar path (pedunculotomy), remaining inferior olivary axons topographically reinnervate the denervated hemicerebellum and compensate functional deficits. Brain-derived neurotrophic factor (BDNF) partly recreates such reinnervation in the mature cerebellum. However the function of this incomplete reinnervation and any unwanted behavioural effects of BDNF remain unknown. We measured olivocerebellar reinnervation and tested rotarod and navigation skills in Wistar rats treated with BDNF/vehicle and pedunculotomized on day 3 (Px3; with reinnervation) or 11 (Px11; without spontaneous reinnervation). BDNF treatment did not affect motor or spatial behaviour in normal (control) animals. Px11-BDNF animals equalled controls on the rotarod, outperforming Px11-vehicle animals. Moreover, Px3-BDNF and Px11-BDNF animals achieved spatial learning and memory tasks as well as controls, with Px11-BDNF animals showing better spatial orientation than Px11-vehicle counterparts. BDNF slightly increased olivocerebellar reinnervation in Px3 animals and induced sparse (22% Purkinje cells) yet widespread reinnervation in Px11 animals. As reinnervation correlated with spatial function, these data imply that after injury even a small amount of reinnervation that is homotypic to correct target neurons compensates deficits in appropriate complex motor and spatial skills. As there was no effect in control animals, BDNF effectively induces this axon collateralisation without interfering with normal neuronal circuits.

Written by huehueteotl

April 7, 2008 at 8:52 am

4 Responses

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  1. Dear Sir,

    Will this study help the patients having cortex cerebral degeneration that is the patients with sequelae of encephalitis ( encephalomyelitis)

    Thanks

    Best Regards,
    Muhammad Ayub -Islamabad-Pakistan

    Muhammad Ayub

    April 8, 2008 at 7:55 am

  2. In 1989 I had a vascular malformation excised from my posterior fossa. The surgery resulted in considerable neurological deficits. What’s worse is that these deficits are continually deepening. Am I a candidate for Brain-derived neurotrophic factor? Nothing else has worked.

    Paul Ostrof

    April 8, 2008 at 6:09 pm

  3. I am really sorry, that I cannot help with any practical information about clinical results in this field of tragical suffering. As I am just reporting findings from a laboratory study of BDNF, I suggest you contact the original article’s authors at the Editors of “Brain” or the research institute Laboratoire de Neurobiologie des Processus Adaptatifs (CNRS/Université Pierre et Marie Curie) that carried out the reported studies. They should be able to provide further information about how and where patients can be enrolled in one of the clinical research projects and what are the actual subjects of clinical research relating to BDNF.

    I wrote a separate reply via E-Mail too.

    All the best

    huehueteotl

    April 9, 2008 at 3:04 pm

  4. Hollo , I had a aneurysm that left me with balance issues .Is there anything I can do to help with my problems?

    Maurice Staton

    July 10, 2016 at 5:13 am


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