Something that stood out to me as I was reading one of the
articles for this week was the role that nitric oxide (NO) plays during
stroke. The review article “Pathobiology
of an ischemic stroke,” notes that the actions of NO seem to contradict each
other, showing that while NO synthesized by a Ca2+ -dependent enzyme
can react to form, “the highly reactive species, peroxynitrate, that promotes
tissue damage,” it also has therapeutic effects, acting to improve the affected
area’s microcirculation to increase oxygen delivery and clean out other
reactive species. The article “Nitric
oxide, ischaemia and brain inflammation,” also notes a similar contradiction.
References to these beneficial effects made me curious as to
whether it would be possible to use NO therapeutically in stroke cases, or if
some substitute could be used that mimics NO’s vasodialatory abilities without
causing an increase in the amount of damaging reactive species. From a quick PubGet search it appears as
though little is being done in this area, as the majority of research is
focused on reducing the production of neuronal nitric-oxide synthase (NOS), the
form of NO that reacts to become the reactive species. One article though did grab my attention. Entitled, “Inhaled nitric oxide reduces
secondary brain damage after traumatic brain injury in mice,” from the Journal of Cerebral Blood Flow and
Metabolism, it describes how researchers used a mouse model to study the
effects of immediate post-injury inhalation of NO on the brain.
Their results were quite promising, specifically noting that
NO inhalation had no effect on NOS levels in the brain, and that secondary
lesion growth was significantly reduced compared to the control group. Now, it should be noted that the mice were
subjected to traumatic brain injury (an injury from an external source), rather
than an embolus as seen in stroke, but as the main effect of both is ischemia,
their results should be relatively transferable. A larger concern would be the ability to
replicate their results in a human study.
This is certainly an area worth further research.
The idea of inhaling NO seemed interesting to me, since we spent quite a bit of time in class talking about the potential idea of intranasal stem cell injection. I was wondering how the traumatic brain injury that the test mice were subjected to was done? I was only able to find the abstract of the paper (I think) that you were referring to, and they didn't explain how it was done but rather just that it was done initially to induce secondary brain damage.
ReplyDeleteI looked up the definition/explanation of traumatic brain injury, and I think this paper did a fair job in explaining it. The reason I wanted to look this up is because that TBI can induce ischemia in the brain in a wide range of severity. I was wondering if the ischemia induced this way, for this particular experiment, resulted in the ischemia seen due to the acquired version via reactive oxygen series?
http://www.ninds.nih.gov/disorders/tbi/tbi.htm
My apologies for not including a source link, I was able to access the article I referenced at Nature, through the UA library. Here's the link: http://www.nature.com/jcbfm/journal/v33/n2/full/jcbfm2012176a.html
ReplyDeleteThe paper goes into more depth about how the injury itself was inflicted. Basically, the researchers performed a craniotomy on the mice, and used an impactor tip to burrow 1mm into the surface of the right parietal lobe to create a lesion.
The paper doesn't address your second question, whether ROS played any role in the ischemia. I would assume that they did not though, as they created a significant lesion and make no reference to ROS. I agree though that the role NO plays in reference to ROS would be an interesting avenue of further research.