Neurohistological applicatons week 1 Flashcards
What is the function of oligodendrocytes?
What is the difference in the function of oligodendrocytes as compared to its equivalent cell type in the PNS?
Oligodendrocytes- myelinate CNS axons; a single oligodendrocyte myelinates multiple axons via concentric layers of the cell’s plasma membrane creating many internodes; this differs from the peripheral NS where one Schwann cell myelinates individual axons.
Unlike Schwann cells in the PNS, oligodendrocytes do NOT surround unmyelinated CNS axons; these are therefore bare and exposed to extracellular fluid.
What is multiple sclerosis? What is one of the major targets of this disease?
What molecule is increased in the CSF and is diagnostic of multiple sclerosis?
Multiple sclerosis is a chronic, inflammatory autoimmune disease. In Multiple Sclerosis there is destruction of the oligodendrocytes and myelin sheath in central axons creating characteristic plaques. Signs and symptoms depend on location of white matter lesions. Myelin basic protein (only in oligodendrocytes, not Schwann cells) is a major autoimmune target. See increased IgG protein (oligoclonal bands) in CSF
What are the different types of foot processes of astrocytes?
What are the functions of astrocytes?
Astrocytes: have numerous stellate processes, some with enlarged foot processes (endfeet) applied to the surface of CNS capillaries (perivascular feet), neurons (perineural feet) or surface of CNS (subpial end processes).
Functions:
- maintain tight junctions between endothelial capillaries forming the blood brain barrier (BBB); selectively restricts certain molecules and protects the CNS from fluctuating levels of hormones, electrolytes and metabolites.
- Maintain ionic environment and control metabolite uptake/distribution.
- Neurotransmitter uptake/metabolism (especially glutamate, major excitatory NT of CNS)
- Couple neuronal activity to blood flow (functional hyperemia)
- glycogen storage which protects against ischemia
- modulate electrical activity at synapses and nodes of Ranvier
How are astrocytes connected to one another?
Astrocyte “syncytium “(formed by gap junctions between astrocytes) so they are electrically coupled; calcium potentials involved in signaling and ATP/ glucose transport.
What forms the blood brain barrier (BBB)?
What is the general function of the BBB?
- Formed by endothelial cells of brain capillaries that are joined by tight junctions (Zonula occludens)
- There are no fenestrations or pores in these capillaries
- The endothelial cells rest on a basal lamina which is surrounded by astrocytic endfeet which helps to maintain the BBB.
- The BBB selectively restricts access (e.g. lipid soluble substances diffuse across it and glucose can cross by facilitated diffusion while other substances of similar size as well as most proteins are excluded.)
What is the implication of the BBB in taking drugs?
The implications of the blood brain barrier are significant in:
restricting access to drugs. Dopamine, for example, cannot be used therapeutically for Parkinson’s disease since it cannot cross the barrier; its precursor L-dopa can cross the barrier where it is then converted to active dopamine. Many antiobiotics cannot cross the BBB.
What is the implication of the BBB in isolating brain tissue from the immune system?
- BBB established in the embryo before immunocompetence and mechanisms for “recognition of self” come into play.
- CNS therefore harbors sequestered antigens subject to autoimmune attack when the BBB is compromised.
- Pathologic events that can break down the BBB include: inflammation, ischemia, tumors, or trauma
- Autoimmune responses may then be superimposed on these events. Example, breakdown of BBB can expose “foreign” central myelin to immunologic attack and cause subsequent demyelination.
What are the 5 areas in which the BBB is modified or absent (i.e. capillaries are fenestrated)?
1) Choroid plexus (for CSF production). CSF is an ultrafiltrate of blood so fenestrated capillaries are needed here.
2) Posterior pituitary and median eminence of the hypothalamus where releasing/inhibitory factors and hormones are dispersed from neuron terminals into bloodstream
3) the pineal gland (for secretion of melatonin)
4) the area postrema in the roof of the 4th ventricle: monitors blood for toxins (e.g. drugs and alcohol) and triggers vomiting when appropriate
5) The Organum Vasculosum of the Lamina terminalis (OVLT): osmotic sensing area of hypothalamus for regulation of osmolarity, ADH, thirst mechanisms, etc.
What is the CNS neurovascular unit? What is the function of it?
What clinical imaging processes is the function of the CNS neurovascular unit the basis for?
The CNS “Neurovascular Unit:” Astrocytic processes are intricately associated with synapses and noed of Ranvier and sample neuronal activity at these sites. Potentials are generated that transmit through the astrocytic nework to the microvessels where they act on arteriolar smooth muscle to increased blood flow to that region.
Such activity dependent changes in blood flow are also the basis for clinical imaging in functional MRI (f-MRI) and SPECT/PET scans for mapping brain activity.
What is the appearance of microglia?
When do microglial cells become active?
How do they respond to conditions that cause them to become active?
What cells are microglia derived from?
- small cells with dark, elongated nuclei
- have migratory and phagocytic properties that become “reactive” during injury, infection or disease (e. g. autoimmune disorders)
- they respond to inflammation and infection by proliferating, migration to affected site, transform into macrophages, and phacocytize pathogens and debris
- are derived from bone marrow monocytes
Where are ependymal cells found?
What is the shape of ependymal cells? What is present on their luminal surfaces and what is the function?
What organelle is numerous in ependymal cells?
How are ependymal cells attached to one another? What is the function of this?
Ependymal cells: columnar cells lining the CSF containing ventricles of brain and central canal of spinal cord. Contain numerous mitochondria. Luminal surface have cilia which circulate the CSF around the CNS. Microvilli are also present and function in absorption. Their base contacts subependymal layer of astrocytic processes. Are attached to each other at junctional complexes (JC) via zonulae adherens (desmosomes) which allows CSF to diffuse into CNS (Thus CSF examination via a spinal tap allows examination of certain infections/diseases)
What cells do ependymomas orginate from? In what location of the brain are they most common in?
Ependymomas
- originate from Ependymal cells
- most common in posterior aspect of brain
- location determines symptoms
- 10% of all childhood CNS tumors are of this type
Note that the ventricle in the attached picture is enlarged due to backed up CSF
Where in the CNS is the choroid plexus?
What cells are in the choroid plexus? What structure is closely associated with cells of the choroid plexus?
Choroid Plexus: Contained within the CNS ventricles and consist of modified ependymal cells associated with adjacent capillary loops where CSF is made and transported.
How many layers is the neocortex composed of?
What is the primary input layer? What part of the CNS inputs to this layer? In what parts of the brain is this layer of the neocortex the thickest?
What is the primary output layer? What cell types are in this layer? In what parts of the brain is this layer of the neocortex the thickest?
- Neocortex has 6 characteristic layers
- Primary input layer is to layer IV from the thalamus which relays sensory information to the cortex; this layer is thickest in primary sensory cortices (e.g. Visual and Primary Somatosensory cortex).
- Primary output layer is layer V which contains large pyramidal cells; in motor areas this layer is very thick. Pyramidal neurons are the most numerous neurons of the neocortex and named for their shape: Conical cell body with long apical dendrite and many basal dendrites that emerge from base of cell and a long axon that project to other CNS regions.
What is the most prominent part of projection neurons? What do projection neurons typically do?
Projection neurons: have long axons typically connecting distant regions of the CNS. Example: Corticospinal neurons from motor cortex to motor neurons in anterior horn of spinal cord
What is the function of commissural neurons?
What are the functions of the anterior commissure (AC) and the posterior commissure (PC)?
Commissural neurons: connect corresponding areas between the right and left hemispheres. Example: fibers in the corpus callosum connect the same cortical areas on both sides.
Anterior Commissure: interconnects 2 temporal lobes
Posterior Commissure: connects two pretectal areas. fibers here involved with consensual pupillary light reflex
What is the function of association neurons?
Association neurons: connect different cortical regions within the same hemisphere; (e.g. areas for language comprehension to motor speech areas)
What type of degeneration occurs when there is injury to a CNS neuron?
What cells sheds myelin debri in the CNS?
What are 2 reasons why myelin removal is slow in the CNS?
CNS Response to Injury: usually CNS neurons cannot regenerate (some exceptions)
Wallerian degeneration occurs distal to site of injury; the oligodendrocyte is involved with shedding myelin debris (as occurs in PNS with Schwann cell)
In the CNS, the BBB is disrupted only at site of injury (not along entire length of injury) which limits infiltration of macrophages, slowing myelin removal
The inefficient clearance of myelin debris is due to:
- limited access of monocyte derived macrophages
- inefficient phagocytic activity of microglia (do not work as well as monocyte derived macrophages)
