Abstract:
:Secondary degeneration is a form of 'bystander' damage that can affect neural tissue both nearby and remote from an initial injury. Partial optic nerve transection is an excellent model in which to unequivocally differentiate events occurring during secondary degeneration from those resulting from primary CNS injury. We analysed the primary injury site within the optic nerve (ON) and intact areas vulnerable to secondary degeneration. Areas affected by the primary injury showed morphological disruption, loss of beta-III tubulin axonal staining, reduced myelinated axon density, greater proteoglycan expression (phosphacan), increased microglia and macrophage numbers and increased oxidative stress. Similar, but less extreme, changes were seen in areas of the optic nerve undergoing secondary degeneration. The CNS-specific L- and T-type calcium channel blocker lomerizine alleviated some of the changes in areas vulnerable to secondary degeneration. Lomerizine reduced morphological disruption, oxidative stress and phosphacan expression, and limited early increases in macrophage numbers. However, lomerizine failed to prevent progressive de-myelination of ON axons. Within the retina, secondary retinal ganglion cell (RGC) death was significant in areas vulnerable to secondary degeneration. Lomerizine protected RGCs from secondary death at 4 weeks but did not fully restore behavioural function (optokinetic nystagmus). We conclude that blockade of calcium channels is neuroprotective and limits secondary degenerative changes following CNS injury. However such an approach may need to be combined with other treatments to ensure long-term maintenance of full visual function.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Fitzgerald M,Bartlett CA,Evill L,Rodger J,Harvey AR,Dunlop SAdoi
10.1016/j.expneurol.2008.11.026subject
Has Abstractpub_date
2009-03-01 00:00:00pages
219-30issue
1eissn
0014-4886issn
1090-2430pii
S0014-4886(08)00466-4journal_volume
216pub_type
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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