Strokes are a common way for a large amount of neurons to die due to vasculature occlusions in the periphery or in the cortical regions that lead to a deprived oxygen and glucose source to the brain. Neurons do not have glucose storages like most cells, so they depend on a constant supply to oxygen and glucose through the blood in order to carry out an oxidative reaction which will allow for the production of ATP and carry out other cellular functions. The lack of oxygen to the brain is known as an ischemic event and some of the most common symptoms are unilateral facial drooping, slurred speech, confusion, and muscle weakness typically on one side of the body as well. If these symptoms are detected on time and the patient is rushed immediately to the hospital, they are able to receive a treatment known as tPA or tissue plasminogen activator which will break the thrombus that is occluding the blood supply to the brain, and symptoms will resolve almost immediately. However, patients who are actively having a stroke will only have a short amount of time to receive this treatment in order to minimize potential neurological deficits. If a patient is out of the time range, which is about 1-4.5 hours after the onset of symptoms, they will no longer be eligible to receive tPA and other treatment options have to be considered such as surgically removing the occlusion. In a lot of cases, patients will suffer from neurological deficits following a stroke.
Neurogenesis is the process by which new neurons are created. This involves an immature neuron proliferating, migrating to a different part of the brain, differentiating, and finish maturing. There has been evidence in post stroke instances where neurogenesis has taken place. Neural stem cells from the subventricular zone (SVZ) and the dentate gyrus, which are typical places where immature neurons can be found, will travel to the damaged area and then differentiate. Although this process sounds effective, there have been some concerns regarding the new neurons ability to survive due to the increase in inflammation and other factors in the brain that take place after a stroke. In majority of cases, inflammation in the brain will prevent neurogenesis from taking place, however, there has been some evidence to show that it can trigger neurogenesis.
Proteins such as SDF-1 and MCPI are involved in inflammation but there has also been evidence to show that these proteins are also associated to the neurogenesis. MMPs, is a particular protein that is involved in the repairing of the cellular matrix after a stroke, and this has been seen to be involved in migration to promote neurogenesis. With this in mind, the timing of inflammation is also an important factor when it comes to neurogenesis. There has been an attempting to target neuroinflammation when trying to target neurogenesis, GSK inhibitors are particularly used but more needs to be researched on these inhibitors.
Another factor that is considered for neurogenesis are microglia. There has been some evidence to show that they are involved in neurogenesis as they can secrete trophic factors which help neurons to survive and migrate. In studies where there is a decrease in microglia, have also demonstrated that there has been a decrease in neurogenesis. There is a similar mechanism observed in angiogenesis where endothelial cells that are closely involved in creating more vasculature secrete trophic factors VEGF, SDF01, and angiopoeitin-1 which have also been seen to be involved in neurogenesis; particularly in the differentiation step and ultimately survival of the newly formed neuron. With this, angiogenesis can also be targeted when attempting to target neurogenesis. Another type of glial cell involved can be the astrocyte as they are neuron precursors. They can release factors that will help neurons survive. Upon division of these astrocytes, a precursor is developed and a neuron will also be created; this has been considered as a potential treatment. It is important to note that many of these discoveries were done on mice and rats who underwent surgical occlusion, there is still more that needs to be investigated in humans.
With neurogenesis, there is an issue that newly formed neurons might not survive. For this, there has been research done using stem cells promote neurogenesis while also helping neurons survive. A study done on mice showed that implanting stem cells into the hippocampus 24 hours after an ischemic episode showed improved recovery when it came to their behavior and also decreasing the size of the infarct, or the area where the stroke took place. Within this same study, it was also noted that the blood brain barrier improved. This same group of researchers also noted that stem cell implantation with tPA showed a decrease in pro-inflammatory cytokines (proteins involved in an inflammatory response), in addition to a decrease in TNF-alpha, and IL-6 which are known to decrease neurogenesis when there are excessive amounts present. However, there are still ethical concerns regarding this potential therapy as many stem cells obtained are human fetal stem cells, so more research has to be done.
The field of neurogenesis is very fascinating as it can be used as a potential treatment following a stroke. There is still more research that needs to be done, but this form of therapy can yield favorable results.
Reference:
Rahman AA, Amruta N, Pinteaux E, Bix GJ. Neurogenesis After Stroke: A Therapeutic Perspective.Transl Stroke Res. 2021 Feb;12(1):1-14. doi: 10.1007/s12975-020-00841-w. Epub 2020 Aug 29. PMID: 32862401; PMCID: PMC7803692.
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