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SUMMARY:Imaging axonal degeneration and regeneration - Martin Kerschenstei
 ner  Institute of Clinical Neuroimmunology\, Ludwig-Maximilians University
  of Munich\, Germany
DTSTART:20090401T124500Z
DTEND:20090401T133000Z
UID:TALK17649@talks.cam.ac.uk
CONTACT:Anna Di Pietro
DESCRIPTION:Damage to axons determines the clinical deficit in many neurol
 ogical conditions including multiple sclerosis and traumatic spinal cord i
 njury. In this presentation I want to introduce new approaches which allow
  us to follow the degeneration and regeneration of single axons in the spi
 nal cord of living animals.\nTo investigate the behaviour of single axons 
 after transaction we have developed an in vivo imaging approach that revea
 ls the sequence of events that unfold after spinal cord injury with high t
 emporal and spatial resolution. Using a combination of modern imaging and 
 transgenic labeling of neuronal subsets we monitor individual fluorescent 
 axons over several days after transection in the spinal cord of living mic
 e. Our results indicate that axonal die-back after transection is mediated
  by an acute form of axonal degeneration which is similar in mechanisms to
  delayed Wallerian degeneration. In vivo imaging further reveals that many
  axons attempt regeneration within 24 hours after lesion. This growth resp
 onse appears to fail due to the lack of directional information. Time-laps
 e imaging of single axons can thus provide a powerful analytical tool for 
 assessing the pathogenesis and therapy of spinal cord injuries. More recen
 tly we have adapted this in vivo imaging approach to investigate the patho
 genesis of immune-mediated axon damage in an animal model of multiple scle
 rosis. By time-lapse imaging of fluorescently labeled axons we could follo
 w the slow and spatially restricted degeneration of axons in inflammatory 
 CNS lesions. This “focal axonal degeneration” appears to be a novel ty
 pe of axonal degeneration that can be differentiated from post-traumatic f
 orms of axonal degeneration like Wallerian degeneration e.g. by its limite
 d extension and slow speed of progression. We could further identify inter
 mediate stages of “focal axonal degeneration” that can persist for sev
 eral days and progress either to the degeneration or full recovery of the 
 affected axons. The early stages of “focal axonal degeneration” are of
 ten associated with persistent macrophage contacts suggesting that macroph
 age-derived mediators play a crucial role for the induction of this proces
 s. \nUsing these models of spinal cord injury and multiple sclerosis I hop
 e to illustrate how in vivo  imaging can help us to understand the pathoge
 nesis of axon injury and pave the way towards the development of targeted 
 neuroprotective therapies. \n
LOCATION:Cripps Court\, Magdalene College
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