Publication Date:
2011-07-15
Description:
Spinal cord injuries often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. The effects of impaired breathing are a leading cause of death from spinal cord injuries, underscoring the importance of developing strategies to restore respiratory activity. Here we show that, after cervical spinal cord injury, the expression of chondroitin sulphate proteoglycans (CSPGs) associated with the perineuronal net (PNN) is upregulated around the phrenic motor neurons. Digestion of these potently inhibitory extracellular matrix molecules with chondroitinase ABC (denoted ChABC) could, by itself, promote the plasticity of tracts that were spared and restore limited activity to the paralysed diaphragm. However, when combined with a peripheral nerve autograft, ChABC treatment resulted in lengthy regeneration of serotonin-containing axons and other bulbospinal fibres and remarkable recovery of diaphragmatic function. After recovery and initial transection of the graft bridge, there was an unusual, overall increase in tonic electromyographic activity of the diaphragm, suggesting that considerable remodelling of the spinal cord circuitry occurs after regeneration. This increase was followed by complete elimination of the restored activity, proving that regeneration is crucial for the return of function. Overall, these experiments present a way to markedly restore the function of a single muscle after debilitating trauma to the central nervous system, through both promoting the plasticity of spared tracts and regenerating essential pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163458/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163458/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alilain, Warren J -- Horn, Kevin P -- Hu, Hongmei -- Dick, Thomas E -- Silver, Jerry -- HL080318/HL/NHLBI NIH HHS/ -- NS060767/NS/NINDS NIH HHS/ -- NS25713/NS/NINDS NIH HHS/ -- R01 NS025713/NS/NINDS NIH HHS/ -- R01 NS025713-25/NS/NINDS NIH HHS/ -- R01 NS060767/NS/NINDS NIH HHS/ -- R01 NS060767-04/NS/NINDS NIH HHS/ -- R37 NS025713/NS/NINDS NIH HHS/ -- R37 NS025713-24/NS/NINDS NIH HHS/ -- England -- Nature. 2011 Jul 13;475(7355):196-200. doi: 10.1038/nature10199.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106, USA. wja4@case.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21753849" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Axons/physiology
;
Chondroitin ABC Lyase/metabolism
;
Chondroitin Sulfate Proteoglycans/metabolism
;
Diaphragm/physiology
;
Disease Models, Animal
;
Electromyography
;
Extracellular Matrix/metabolism
;
Nerve Net/physiology
;
Nerve Regeneration/*physiology
;
Neuronal Plasticity/physiology
;
Phrenic Nerve/cytology/physiology/surgery/transplantation
;
Rats
;
*Respiration
;
Spinal Cord Injuries/*physiopathology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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