Nitric oxide is normally a part of the brain’s mechanisms. It functions as a neurotransmitter to either promote or block signals between neurons. However, damage to glial cells results in an uncontrolled increase in nitric oxide. Glial cells are the support system cells of the central nervous system. When they are damaged it can lead to damage to the neurons and dysfunction of cognitive processes, such as is present after traumatic brain injury through release of proinflammatory molecules including nitric oxide. Nitric oxide is involved in the process of inflammation which is usually a good thing when tissues are damaged; think of if you hurt your hand. In that instance, inflammation is good and helps promote healing. However, in your brain, there is not much room for the expansion of tissue due to increased blood flow and fluid associated with inflammation and the cells affected (neurons and glial cells) are very sensitive to the chemical changes following injury. Therefore, inflammation in the brain quickly leads to cell injury and death in populations of cells that are often difficult or impossible to replace. This type of inflammation can occur with near all neurological conditions from head injury to multiple sclerosis.
The damaged caused by nitric oxide in the brain is wide reaching and significant. It can include upregulation of reactive nitrogen species which further damage tissue and promote inflammation. It may also decrease mitochondrial function to decrease the ability of the cell to produce enough energy to live. Finally, nitric oxide can both lead to vasodilation (increasing the diameter of the blood vessels entering the brain) and disrupting the blood brain barrier. This results in a rush of unfiltered blood into the brain carrying with it more immune cells as well as possible toxins. In these ways, increased nitric oxide following injury or in a disease state can exacerbate the condition and symptoms.
Because of the beneficial signaling involving nitric oxide throughout the body, including the brain, it is not appropriate to try to completely eradicate nitric oxide, its precursors, or the enzymes that make it. Often times, genetically modified animals without these genes (called knockouts) do not survive long because important pathways that use nitric oxide, but unrelated to inflammation, also cannot happen. Therefore, to utilize the presence of nitric oxide in an injured environment to aid in diagnosis and/or treatment of neurological condition, it must be targeted specifically in the immune cells that cause the damage in the inflamed brain, especially glial cells.
The story of nitric oxide: when does it become bad?
