NO in cerebral ischaemia: hate it or love it

In the article, Nitric Oxide, ischaemia and brain inflammation, nitric oxide and nitric oxide synthase (NOS) isoforms are shown to be implicated in stroke pathophysiology. In a cell, nitric oxide can mutate DNA, inhibit the electron transport chain, and either promote or protect the cell from apoptosis. There are three isoforms of NOS: neuronal NOS-1, inducible NOS-2, and endothelial NOS-3. All isoforms have been shown to increase with cerebral ischaemia. The article focuses on NOS-2 and explains that it has been shown to increase after ischaemia, because cytokines like IL-1beta and TNF-alpha induce NOS-2 transcription. An interesting find in the article, is that NO from NOS-1 and NOS-2 has been shown to be detrimental, however NO from NOS-3 has been shown to be beneficial. Therefore, it is important to try to find treatments to protect the brain from NOS-2 after a stroke. When looking at medications that inhibit NOS, it was found that selective inhibitors were more beneficial than non-selective inhibitors to lessen the deleterious effects of cerebral ischaemia. Other therapeutic options may include pharmaceutical NO donors, which are still under investigative study, preconditioning neurons to help them withstand the effects of ischaemia, and administration of estrogen and/or progesterone, which have shown to reduce lesion volume and improve cognitive function after ischaemia. What I found to be really interesting and cool is that new neurons can differentiate after having a stroke and NO donors have shown to increase neurogenesis. This helps the brain recover from a stroke, which usually have very damaging effects on the brain.