Linked Life Data

19968758

Source:http://linkedlifedata.com/resource/pubmed/id/19968758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-2-9
pubmed:abstractText
Acute axonal shear and stretch in the brain induces an evolving form of axonopathy and is a major cause of ongoing motor, cognitive and emotional dysfunction. We have utilized an in vitro model of mild axon bundle stretch injury, in cultured primary cortical neurons, to determine potential early critical cellular alterations leading to secondary axonal degeneration. We determined that transient axonal stretch injury induced an initial acute increase in intracellular calcium, principally derived from intracellular stores, which was followed by a delayed increase in calcium over 48 h post-injury (PI). This progressive and persistent increase in intracellular calcium was also associated with increased frequency of spontaneous calcium fluxes as well as cytoskeletal abnormalities. Additionally, at 48 h post-injury, stretch-injured axon bundles demonstrated filopodia-like sprout formation that preceded secondary axotomy and degeneration. Pharmacological inhibition of the calcium-activated phosphatase, calcineurin, resulted in reduced secondary axotomy (p < 0.05) and increased filopodial sprout length. In summary, these results demonstrate that stretch injury of axons induced an initial substantial release of calcium from intracellular stores with elevated intracellular calcium persisting over 2 days. These long-lasting calcium alterations may provide new insight into the earliest neuronal abnormalities that follow traumatic brain injury as well as the key cellular changes that lead to the development of diffuse axonal injury and secondary degeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1147-55
pubmed:meshHeading
pubmed-meshheading:19968758-Animals, pubmed-meshheading:19968758-Axotomy, pubmed-meshheading:19968758-Calcineurin, pubmed-meshheading:19968758-Calcium, pubmed-meshheading:19968758-Cells, Cultured, pubmed-meshheading:19968758-Cerebral Cortex, pubmed-meshheading:19968758-Embryo, Mammalian, pubmed-meshheading:19968758-Enzyme Inhibitors, pubmed-meshheading:19968758-Extracellular Space, pubmed-meshheading:19968758-Immunosuppressive Agents, pubmed-meshheading:19968758-Microscopy, Electron, Scanning, pubmed-meshheading:19968758-Neurofilament Proteins, pubmed-meshheading:19968758-Neurons, pubmed-meshheading:19968758-Rats, pubmed-meshheading:19968758-Rats, Wistar, pubmed-meshheading:19968758-Stress, Mechanical, pubmed-meshheading:19968758-Tacrolimus, pubmed-meshheading:19968758-Thapsigargin, pubmed-meshheading:19968758-Time Factors, pubmed-meshheading:19968758-Tubulin
pubmed:year
2010
pubmed:articleTitle
Initial calcium release from intracellular stores followed by calcium dysregulation is linked to secondary axotomy following transient axonal stretch injury.
pubmed:affiliation
NeuroRepair Group and Wicking Dementia Research and Education Centre, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. jerome.staal@utas.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't