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NFL, MMA, etc.) Any single blow to head can increase risk, but repeated blows are worse Immediate effects : Tissue damage, diffuse axonal injury Multiple blow effect lead to a damaging chain reaction Release of Reactive Oxygen Species in massive amounts that damage the Meninges that form a protective barrier around the brain = cell death A little of reactive oxygen species can damage DNA that you can usually repair this, but if not it can lead to cancer But a huge burst of it leads to a defensive mechanism to preemptively kill cells before they mutate and cause cancer (similar to what you do with radiation treatments for cancer) Astrocytes also start to die and they make up the Blood Brain Barrier which begins to leak potassium, sodium and chloride which enter the brain causing the brain itself to swell Next microglial cells get activated to try plug in the hole, but that is part of a big immune response = inflammation Inflammation in the brain leads to accumulation of Amyloid Beta Plagues Amyloid beta plagues are one of the major pathologies associated with Alzheimers It Generally builds up bit by bit as we age over time, but TBI can trigger them much more quickly Plaque levels are formed immediately in TBI akin to rapid aging Amyloid beta forms in between glial cells/neuron forming plaques that disrupt glucose metabolism, create even more reactive oxygen species, immune system/inflammation and have this vicious cycle of more and more damage Tau proteins (other key sign of developing Alzheimers) also dont function correctly leading to mitochondria dysfunction correctly synapses start dying If you cant build synapses, you cant learn and brain atrophies In general, cells are already stressed and now they are more susceptible to death (similar to when cells choose to die rather than become cancerous by releasing pro-apoptotic proteins ) Note: Some cancers have figured out how to prevent this by expressing these anti-apoptotic proteins Stress plus stress is additive, especially in a short timeframe Joe has seen it during a fight, a guy started off one way and came out different and less able to communicate later One TBI can create damage which can continue for months after the original trauma Energy Triage : Everything in your body requires energy and when there is chronic/major damage due to anything (e.g
Schaller, M
Crosses the Blood-Brain Barrier Unlike many peptides and growth factors, Dihexa is orally bioavailable and crosses the BBB , meaning it can be taken as an oral tablet and still reach brain tissues in therapeutic concentrations
the accession code for the raw mass spectrometry data (in Fig
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