Lactate; Brain Damage
13:08 – Lactate buildup in the brain when the brain is deprived of oxygen. Astrocytes are a type of supporting cell in the brain and they account for 50% of the brain volume. These astrocytes create energy in a way that doesn’t use the mitochondria and therefore does not require oxygen; this process also produces lactate. Lactate is a great source of energy for other cells in the brain, but if oxygen is not present, then these cells cannot turn lactate into energy. Thus, lactate will build up in the brain and can do damage to other cells.
16:38 – The link between a blow to the head and the alzheimer’s-like effects that follow. Multiple repetitive injuries lead to tissue damage and reactive oxygen species are released. [we have talked a lot about reactive oxygen species in previous summaries – Dr. Patrick sheds some much needed light on this subject]. We constantly release reactive oxygen species, but at a small rate compared to what happens when tissue is damaged in the brain.
Programmed Cell Death
18:08 – When DNA is being damaged at an above average rate, the body no longer seeks to repair the damage and instead kills off the cell. The body does not want the excessive damage to lead to a mutation and possibly cancer. This is the same reasoning for using radiation to kill cancer cells, there is too much damage at once and thus cell death occurs rather than an attempt to repair damage.
19:10 – Cell death as a result of an increase of reactive oxygen species can lead to astrocytes deaths elsewhere in the brain. These astrocytes make up the blood-brain barrier an if these cells diminish, then the barrier becomes leaky, allowing easy access for potassium, sodium, chlorine and water. This influx of material can cause the astrocytes to swell – leading to edema.
Microglia Cells; Immune Response
21:34 – Dead cells in the brain lead to microglia cells rushing from the rest of the body towards the blood brain barrier attempting to close of leaks. This is an immune response that, as we shall see, leads to many problems.
22:08 – The microglia also try and ‘eat up’ cellular debris that remains from the cells dying en masse. This clean up process causes inflammation in the brain. Within hours of an sever injury, the brain begins to accumulate amyloid beta plaques as a result of the microglia response.
Amyloid Beta Plaque
23:23 – Amyloid beta plaque in detail. Amyloid beta plaques are a major pathology associated with alzheimer’s. These plaques form outside of neurons and this disrupts glucose metabolism and creates even more reactive oxygen species (a vicious cycle). On top of that, the microglia cells try and clean the plaque, this causes more plaque. This does not have to come from brain trauma, this cycle can become a huge problem after 7 or 8 decades of just being alive.
25:28 – Tao protein. This protein (found inside the neuron) transports material around the brain and is essential for healthy brain function. The immune response activated after a traumatic brain injury or the increased microglia cell activity as a result of aging, causes these tao proteins to aggregate and it can no long transport its cargo. The train became derailed. Synapses start to die and thus these cells have no purpose and die – this is brain atrophy. We can see this in cases of severe brain injury and in alzheimer’s patients.
27:19 – The accumulation of amyloid beta plaque and the tao protein tangles are two prominent features of alzheimer’s. They cause inflammation and reactive oxygen species to be generated and lead to a cycle that won’t stop.
28:18 – Dr. Patrick explains pre-apoptotic proteins. These proteins exist to signal to the cell that it may be ready to die. There are also anti-apoptotic proteins; the levels of both proteins determine whether the cell will die. In the context of the podcast, an injury will increase the amount of these pre-apoptotic proteins, priming the cells for death. However some may not reach the threshold necessary for immediate death, but they are close. Another injury would most certainly cause surrounding cells to pass the anti-apoptotic/pre-apoptotic threshold, resulting in massive cell death.