alexa Vulnerability of central neurons to secondary insults after in vitro mechanical stretch.


Journal of Spine

Author(s): Arundine M, Aarts M, Lau A, Tymianski M

Abstract Share this page

Abstract Mild traumatic brain injuries are of major public health significance. Neurons in such injuries often survive the primary mechanical deformation only to succumb to subsequent insults. To study mechanisms of vulnerability of injured neurons to secondary insults, we used an in vitro model of sublethal mechanical stretch. Stretch enhanced the vulnerability of the neurons to excitotoxic insults, causing nuclear irregularities, DNA fragmentation, and death suggestive of apoptosis. However, the DNA degradation was not attributable to classical (caspase mediated) or caspase-independent apoptosis. Rather, it was associated with profound stretch-induced mitochondrial dysfunction and the overproduction of reactive oxygen species (ROS). Sublethally stretched neurons produced surprisingly high levels of ROS, but these in isolation were insufficient to kill the cells. To be lethal, the ROS also needed to combine with nitric oxide (NO) to form the highly reactive species peroxynitrite. Peroxynitrite was not produced after stretch alone and arose only after combining stretch with an insult capable of stimulating NO production, such as NMDA or an NO donor. This explained the exquisite sensitivity of sublethally stretched neurons to a secondary NMDA insult. ROS scavengers and NO synthase (NOS) inhibitors prevented cell death and DNA degradation. Moreover, inhibiting neuronal NOS activation by NMDA using peptides that perturb NMDA receptor-postsynaptic density-95 interactions also reduced protein nitration and cell death, indicating that the reactive nitrogen species produced were neuronal in origin. Our data explain the mechanism of enhanced vulnerability of sublethally injured neurons to secondary excitotoxic insults and highlight the importance of secondary mechanisms to the ultimate outcome of neurons in mild neurotrauma. This article was published in J Neurosci and referenced in Journal of Spine

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 18th Global Neurologists Annual Meeting on Neurology and Neurosurgery
    Nov 13-15, 2017, Athens, Greece
  • 2nd International Conference on Pediatric Neurology  
    August 31-September 01, 2017 Prague, Czech Republic
  • 12th Global Neurologists Annual Meeting on Neurology and Neurosurgery
    November 16-18, 2017 Lisbon, Portugal

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version