DAI- from molecules to humans
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1
Uppsala University Hospital, Neurosurgery, Sweden
Axonal injury is a major contributor to the cognitive and behavioral deficits observed in patients with traumatic brain injury (TBI). Although diffuse axonal injury (DAI) is a well-recognized clinical entity, injury to axons is increasingly being observed also in patients with a predominately focal lesion and/or milder forms of TBI. Unfortunately, CNS axons do not spontaneously re-grow in meaningful numbers following injury due to e.g. a lack of growth-promoting factors, the presence of a glial scar and expression of growth-inhibitory molecules. Known endogenous inhibitors to axon regeneration present in myelin include Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp). Nogo-A, MAG and OMgp all bind to the same receptor, the Nogo-66 receptor (NgR1) which has several co-factors including Lingo-1. Since axons fail to regenerate (and lost neural cells cannot be replaced) following TBI, it is surprising that patients frequently show a degree of improvement that likely results from brain reorganization (plasticity). We hypothesize that pharmacological treatments promoting axon regeneration and/or brain plasticity may be a clinically-relevant strategy when attempting to improve the outcome of TBI patients. Here, our experimental approach to animal modeling and behavioral evaluation of TBI is described and biomarker data from severely brain-injured patients are presented. Additionally, data from recent studies evaluating genetic and pharmacological neutralization of endogenous inhibitors to axon regeneration are presented.
Keywords:
axonal injury,
Lingo-1,
Nogo-66 receptor,
Nogo-A,
plasticity,
Traumatic Brain Injury
Conference:
Karolinska Institutet 200 years anniversary
Symposium on Traumatic Injuries in the Nervous System, Stockholm, Sweden, 15 Sep - 16 Sep, 2010.
Presentation Type:
Presentation
Topic:
Traumatic Injuries in the Nervous System
Citation:
Marklund
N
(2010). DAI- from molecules to humans.
Front. Neurol.
Conference Abstract:
Karolinska Institutet 200 years anniversary
Symposium on Traumatic Injuries in the Nervous System.
doi: 10.3389/conf.fneur.2010.56.00009
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Received:
03 Sep 2010;
Published Online:
21 Sep 2010.
*
Correspondence:
Dr. Niklas Marklund, Uppsala University Hospital, Neurosurgery, Uppsala, Sweden, Niklas.Marklund@neuro.uu.se