Lecture 16- Other Brain Cells Flashcards
What is the role of astrocytes in non-inflammatory conditions?
- One end of astrocyte goes to the vascular. Astrocyte end foot= part of the blood brain barrier. In this way helps prevent infection in the brain by creating segregation.
- Other processes of the astrocyte are involved at synapses providing metabolic support (pump lactate as cells releasing glutamate require energy) and clearing neurotransmitter. They are also invovled in potassium buffering (maintaining homeostasis).
What is the role of astrocytes in inflammatory conditions?
- Reactive astrocytes become branches/ fuzzy because they form a scar that limits the access to neurons from the blood.
- Compensate for leaky blood brain barrier/ malfunction that is the result of certain conditions.
How do glial scars compare in healthy tissue, moderate astrogliosis and severe astrogliosis? How is this shown using immunohistochemistry?
Glial scar is shown in immunohistochemistry by staining glial fibrillary protein (GFAP). The extent/ density of this increases across the three tissue conditions. Basically the more densely packed the harder it is for things to get through (stronger the reinforcement around blood-brain barrier becomes). Severe astrogliosis means there is chronic inflammation.
How does the blood brain barrier look in a Nissl stain?
Doesn’t expresses DNA + RNA. Therefore is just a blurry/ clear line in TEM
What are the different components of the blood-brain barrier?
- Composed of endothelial cells (interior) and pericytes (cells around the outside/ next to)
- Basal lamina= fibrous membrane around whole thing
- Then astrocyte end-feet
- Tight junctions forms impermeable barrier
How do reactive astrocytes become glial scars?
- Various things can cause astrocytes to become active (Hypertrophy or Gliogenesis)
- Once activated astrocytes start to migrate together and proliferate forming the glial scar
- Increasing degrees of damage causes this transformation to happen more and more/ to a larger extent.
What is the astrocytic response to CNS injury?
- During head injury: blood brain barrier becomes leaky
- Astrocytes become separated. Macrophages can pass through that shouldn’t be in the brain. Microglia detect this and respond also entering into the brain. There are things in the brain that shouldn’t be!
- Astrocytes respond: become proliferate + become bigger to close gaps in the BBB and stabilize the synapses of nearby neurons.
- They can then perform phagocytosis to clean up neurons that have been damaged (received too much signaling).
- Basically the astrocytes try to limit damage, protect what is there + limit new things coming in
Is there any CNS disease that does not involve astrocytes?
No, they are constantly listening and responding to neurons therefore it something goes wrong with neurons it is likely due to a malfunction of the astrocytes.
What are the 5 neuroprotective functions of reactive astrocytes?
- Debris clearance (phagocytosis)
- Blood Brain Barrier (repairing leaks, limit access)
- Glial scar (physical barrier to prevent peripheral immune cells getting in)
- Inflammation (secret anti-inflammatory factors and suppress pro- inflammatory signaling mechanisms).
- Glutamate ecotoxicity (sequestering of excess glutamate)
Neurons require a lot of energy… how do astrocytes provide this and what transporters do they have to carry out this function?
- Astrocytes transport monocarboxylates (e.g. lactate) to neurons. Note: can just get lactate directly via vasculature in which case in goes through MCT1 at the vessel and then MCT4 to get into astrocyte or astrocytes get glucose via GLUT1 and it’s converted to lactate via glycolysis
- Astrocytes have MCT4, neuron cell bodies have MCT2 and axons have MCT1 to allow this
Does the brain just have a few blood vessels or does it have many?
Many, you could make out the entirety of the brains structure just from a model of the blood vessels. The network is dense.
How was the blood brain barrier discovered?
- Inject blue dye into mouse vasculature: stains tissues that the blood gets into. Brain doesn’t take up dye because of BBB.
- Then if you inject the dye into just the brain again it stays the tissue due to vasculature of brain but not the rest of the body.
- Therefore, there is a clear segregation between the brain and rest of the body in terms of the vasculature that exists.
How does a normal blood vessel and a brain blood vessel differ in terms of what can pass through?
- Normal blood vessels are a lot more leaky. They have gaps/ pore passages and lipid substances can diffuse soluble directly across.
- Vessels in the brain are a lot more selective about what is let through. Carrier-mediated transport is essential in getting any vital nutrients across that can’t just diffuse. Any drugs that get through diffuse due to being extremely small/ lipophilic or by hijacking one of the carrier-mediated transport mechanisms.
What are the 6 limited mechanisms for transport across the BBB?
- Paracellular transport: water soluble agents through tight junctions.
- Diffusion: lipid soluble agents such as antidepressants, alcohol, nicotine
- Protein transporters: for things like glucose, amino acids, nucleosides etc., requires energy. These transporters can be highjacked by things being chemically similar to the normal substrate.
- Receptor-mediated transcytosis: insulin, transferrin, interleukins
- Adsorptive transcytosis: albumin, other plasma proteins. Involves the folding of the cell membrane to take stuff in.
- Efflux transporters: for things like cetirizine. Taking things from the inside and dumping it on the outside.
What is the difference between endothelial cells and pericytes?
Endothelial cells: Central component of BBB. Interface between blood and brain
Pericytes: Regulate how permeable BBB is. Immune function
