Exam 1 Flashcards
(140 cards)
1
Q
What comprises the PNS?
A
Spinal (sensory and motor) nerves
Sensory ganglia
Schwann cells
Autonomic nervous system
Sympathetic
Parasympathetic
Enteric
2
Q
What are the cell types in the CNS?
A
Nerve cells (neurons)
Supporting cells (glia)
Astrocytes, oligodendrocytes, microglia
Capillaries
Ependymal cells
3
Q
What makes up a neuron?
A
A nerve cell has one or more dendrites, a cell body (soma), at most, one axon
4
Q
How are microtubules organized in the cell body and dendtites of the neuron?
A
In both of these structures the microtubules are organized any which way they like.
5
Q
How are microtubules organized in the axon?
A
All in the same direction. The negative side is towards the cell body and the positive side is towards the end terminal of the axon.
6
Q
What is one reason for the structural/functional polarization of neurons as a whole?
A
The unified polarization of microtubules within the axon.
7
Q
What are the three subtypes of neurons by structure?
A
Multipolar neuron- dendrites on cell body and one axon coming off. (most abundant)
Bipolar neuron- Cell body in middle with processes protruding out on either side. One end is the receiving end and the other end is the signalling or information transfer end. These are found in the retina and the 8th cranial nerve (auditory vestibular).
Unipolar neurons- Cell body looks like a flower sticking up from the ground. These are found in the sensory ganglia.
8
Q
What are the output cells of the cerebral cortex?
A
Pyramidal cells.
9
Q
How can you break down neurons based on branching shape?
A
ie. pyramidal and stellate
10
Q
How can you break down neurons based on axon size?
A
Long axon projection neurons
to other neurons
to effectors (muscles, glands)
Short axon interneurons (aka local circuit neurons)
Amacrine cells
11
Q
Where are amacrine cells primarily located?
A
The retina. They have no axon.
12
Q
What is an LCN?
A
A local circuit neuron or short axon neuron.
13
Q
What is the end of an axon called?
A
The telodendron. At the end of each terminal branch in this telodendronic region, there is a button called the terminal bouton.
14
Q
What is contained within the terminal boutons?
A
2 main things= mitochondria and synaptic vessicles containing neurotransmitters.
15
Q
What are the 3 basic ingredients in a synapse?
A
Axon terminal (presynaptic), gap in between called the synaptic cleft, and receiving portion of dendrite (PSD)
16
Q
What distinguishes motor neurons histologically?
A
They stain nice with a silver stain but are most known for their clumps of nissle bodies (rough ER)
17
Q
What neurons are vulnerable to the polio virus?
A
Motor neurons in the spinal cord
18
Q
What are lower motor neurons?
A
Motor neurons in the spinal cord. As opposed to motor neurons further up in the nervous system that are the commanders of these.
19
Q
How does Parkinson’s manifest on a histological slide?
A
Neuromelanin is a biproduct of dopaminergic signaling and appears black on the section. A healthy brain will show black in the substantia nigra while this coloring will diminish or disappear in a Parkinson’s patient’s section.
20
Q
How does Huntington’s manifest on a histological slide?
A
Huntington’s is characterized by a regional degeneration and subsequent expanding of the nearby ventricles.
21
Q
How does Alzheimer’s manifest on a histological slide?
A
Marked hippocampal degredation initially and utlimately global degredation. (am beta plaques and phos tau tangles)
22
Q
What are the 3 types of cell death?
A
Apoptosis, necrosis, autophagy
23
Q
What do astrocytes do?
A
They provide structural and metabolic support, contribute to the blood-brain barrier, form CNS scars, provide scaffolding for neuronal migration and axon guidance, may participate in signal processing and memory encoding
24
Q
What do oligodendrocytes do?
A
They form CNS myelin
25
What do microglia do?
They're the macrophages of the CNS
26
What is one key function of astrocytes?
The BBB
27
How do astrocytes contribute to the BBB?
Astrocytic endfeet make a wall around the outer wall of the capillary. Endfeet are the outermost covering of the BBB.
28
What is the point of the Nodes of Ranvier?
Electrical conduction jumps from node to node vastly speeding up conduction down the axon. Sultatory conduction. The electrical signal doesn't have to change the membrane potential at every point, only the nodes of ranvier.
29
What myelinates PNS cells?
Schwann cells.
30
How does schwann cell myelination differ from regular?
Schwann cell throws its whole body into it. It then extrudes the cytoplasm.
31
What is one place shwannomas are very common?
The point of entry of the 8th cranial nerve into the brainstem.
32
Where are action potentials initiated?
The spike initiation zone is usually located near the axon hillock, where the axon emerges from the cell body.
33
What are granule cells?
Granule cells are smaller, and are often star-shaped (stellate) because the dendritic tree radiates out in all directions from the soma. Granule cells provide much of the local (regional) information processing.
34
What are pyramidal cells?
Pyramidal cells vary in size, but have a stereotypical shape: a pear-shaped soma, several dendrites (called basal dendrites) emerging from the base of the soma, a large and highly branched dendrite emerging from the apex of the soma (called the apical dendrite), and an axon that issues from the base of the cell body. The dendrites of most pyramidal cells have structural embellishments called dendritic spines
35
What's another name for long axon neurons?
Projection cells
36
Many interneurons are?
Inhibitory
37
Describe the neuromuscular junction.
Motor neurons innervate skeletal muscles at neuromuscular junctions, which are a specialized version of a synapse. These contacts form a motor end plate consisting of an enlarged axon terminal containing synaptic vesicles, junctional folds, an enlarged synaptic cleft, and the muscle sole plate.
38
What are the two types of activated microglia?
Activated microglia exist in two forms: non-phagocytic microglia are immediately responsive to CNS inflammation, while activated phagocytic microglia comprise the most immune-responsive form of the cell.
39
How do axtivated phagocytotic microglia work?
Activated phagocytic microglia phagocytose apoptotic neurons during CNS development, and respond to trauma and toxic lesions/material in the adult CNS. To do so, the activated phagocytic microglia migrate to the site of injury, phagocytose the foreign material, and secrete pro-inflammatory factors that promote proliferation of additional microglia. As a part of this response, the activated phagocytic microglia can activate astrocytes and impact capillary endothelial cells, aiding the response to infection. However, prolonged microglial activation can directly or indirectly damage neurons through the chronic release of soluble factors associated with the inflammatory response. This is thought to occur in many neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, as well as viral (HIV, HSV), bacterial (Streptococcus pneumoniae) and parasitic (Plasmodium falciparum) infections.
40
What do astrocytes do?
Astrocytes provide structural and metabolic support for neurons, participate in the regulation of ions and molecules in the extracellular fluid, contribute to the blood-brain barrier, form CNS scars, provide scaffolding for neuronal migration and axon guidance during development, and may participate in signal processing and memory encoding. There are two subtypes: fibrous (found in white matter) and protoplasmic (found in gray matter)
41
Why is white matter white?
Because myelin has a very high lipid content, myelinated axons appear white. For this reason, myelinated fiber tracts are called white matter, in contradistinction to CNS regions with high concentrations of cell bodies, which are called gray matter.
42
What is a neurotransmitter?
In classic terms, neurotransmitters are small molecules that are synthesized within neurons, packaged into synaptic vesicles, and released by nerve terminals into the synapse in response to nerve impulses (or action potentials) invading the terminals. In reality, the distinction between such classic neurotransmitters and many other types of chemical signals is arbitrary, as will be seen.
43
What are the 7 steps in chemical synaptic transmission?
1. Nerve impulse (action potential) invades presynaptic nerve terminal.
2. Activation of Ca2+ channels and entry of Ca2+ into nerve terminal.
3. Ca2+ triggers neurotransmitter release via exocytosis.
4. Released neurotransmitter activates pre- and postsynaptic receptors.
5. Receptor activation regulates ion channels to yield postsynaptic currents.
6. Released neurotransmitter is removed from synapse.
7. Vesicles involved in exocytosis are recaptured by endocytosis.
44
What role do astrocytes play in synaptic transmission?
Glial cells, in particular, astrocytes, play crucial roles in synaptic transmission. For example, most classic (glutamtergic) synapses are surrounded by astrocytes, which buffer extracellular levels of glutamate and thereby protect neurons from excessive excitation which can kill neurons through excitotoxicity.
45
What are the basic steps of exocytosis?
A neurotransmitter is packaged into synaptic vesicles via a vesicular transport protein present on the vesicle membrane. Vesicles are poised for release (docking and priming) by binding to the active zone on the nerve terminal plasma membrane. Ca2+ entry then triggers fusion, which allows neurotransmitter release. The vesicle is then recaptured via endocytosis, which is dependent on the protein clathrin.
46
What are the amino acid nts?
Glutamate
GABA (γ-aminobutyric acid)
Glycine
47
What are the monoamine nts?
```
Catecholamines
Dopamine
Norepinephrine (also known as noradrenaline)
Epinephrine (also known as adrenaline)
Indoleamines
Serotonin
Melatonin (in pineal gland only)
Acetylcholine
Histamine
```
48
What are some species that exert nt like properties but are not necessarily considered to be nts?
Nucleosides Adenosine
ATP
Many others (di-, trinucleosides, etc.)
Lipid-derived Anandamine, 2AG (2-arachidonoylglycerol)
Gases Nitric oxide (NO)
Neurotrophic factors Neurotrophins (e.g., BNDF [brain-derived neurotrophic factor])
Many other growth factors and cytokines
```
Hormones with Steroid hormones
nuclear receptors Glucocorticoids
Gonadal steroids
Retinoic acids
Thyroid hormone
Vitamin D
```
49
Which nts activate ligand-gated channels that pass Na+ and what does this lead to?
Glutamate, acetylcholine, serotonin, and nucleosides. These lead to excitatory postsynaptic currents.
50
Which nts activate ligand-gated channels that pass Cl- and what does this lead to?
GABA and glycine. This leads to inhibitory postsynaptic currents.
51
What determines whether a channel passes anions or cations?
The charges of amino acids that face the pore determine whether the channel passes cations or anions.
52
What are the two main modes of neurotransmission?
Ligand-gated channels (“ionotropic receptors”) and G protein-coupled receptors or GPCRs (“metabotropic receptors”)
53
What are the differences in the transmembrane domains of ligand gated versus GPCRs?
Ligand-gated channels have 4 transmembrane domains while GPCRs have 7. G proteins interact with the GPCR’s C-terminus and 3rd cytoplasmic domain.
54
How do neurotrophic factors work?
Virtually all neurotrophic factors act by binding to plasma membrane receptors which lead, directly or indirectly, to the activation of protein tyrosine kinases (which phosphorylate substrate proteins on tyrosine residues only). In some cases, the neurotrophic factor receptors contain tyrosine kinase activities: the receptors are in essence ligand-activated tyrosine kinases.
55
How do steroid hormones and related signals work?
Steroid hormones and related signals diffuse passively into a neuron’s cytoplasm where they bind to cytoplasmic receptors (referred to nuclear hormone receptors). The binding triggers the transport of the receptor into the nucleus where the protein functions as a transcription factor. This can lead to the same types of long-lasting plasticity induced by classic neurotransmitters as noted above.
56
What is the resting membrane potential driven by?
K+ Channels.
57
Movements of any permeable ion across the membrane are driven by?
The electrostatic attraction or repulsion by the charges inside of the cell
The concentration gradient, which is created by pumps and transporters
58
What are the net flows of the 4 major ions within the physiological ranges?
K+ outward
Na+ inward
Ca2+ inward
Cl- outward
59
Under what conditions are Cl- currents inward (depolarizing)?
* When the membrane is very well polarized
* When intracellular Cl- is relatively high, making the Cl- reversal potential less negative. This occurs during development, and in some dendrites.
60
What is capacitance?
All membranes have a property called capacitance, which is the ability to redistribute charges within the membrane. The effect of capacitance is to slow the voltage response to a current.
A sustained current (typically about 50 ms long) will generate a voltage in accordance with Ohm’s law (V = IR). However, a brief current will produce a smaller voltage.
61
Why does the muscle unit at the NMJ reliably contract in response to every presynaptic potential?
1) On the presynaptic side, there is a very high probability of acetylcholine release in response to a single spike arriving at the nerve terminal.
2) The extensive surface area of the postsynaptic membrane present a large number of nicotinic AChRs to transmitter in the cleft.
62
What is expected of a mechanism for memory formation?
Must occur under conditions of learning – for example, when two experiences reliably occur together (think of Pavlov’s dogs)
Must be capable of very rapid formation (think of the first time you met someone memorable)
Must be stable (for decades!)
63
What is glutamate?
The major excitatory neurotransmitter in brain
• Over 40-50% of all neurons utilize glutamate as a transmitter.
Glutamate is involved in every aspect of brain function.
Glutamate is ubiquitous; only a minute fraction of neuronal glutamate is packaged into vesicles to act as a neurotransmitter.
64
What are the two main classes of glutamate receptors?
Two major classes of glutamate receptors:
Ligand-gated Na+(Ca2+) channels GPCRs (“metabotropic
receptors")
AMPA mGluR1-8
NMDA
Kainate
Mediate rapid neurotransmission Exert more
Modulator effects
Serve as an
autoreceptor
65
What is GABA?
The major inhibitory neurotransmitter in brain and spinal cord.
• 40-50% of all neurons in brain utilize GABA as a transmitter.
• As such, plays major role in regulating level of consciousness.
GABA is involved in every aspect of brain function.
GABA is synthesized from glutamate via the enzyme, glutamatic acid decarboxylase (GAD) and degraded by GABA transaminase.
66
What are the two major classes of GABA receptors?
Two major classes of GABA receptors:
Ligand-gated Cl- channels GPCRs (“metabotropic
receptors")
GABAa GABAb
GABAc
Mediate rapid neurotransmission Exert more
Modulatory effects
Serve as an
Autoreceptor
67
What does Glycine do?
Along with GABA, the major inhibitory neurotransmitter in the spinal cord.
• Blockers of glycine receptors, e.g., strychnine, are convulsants (induce seizures).
68
What are the major classes of glycine receptors?
```
There is only one major class of glycine receptor: a ligand-gated Cl- channel
• This is called the “strychnine-sensitive glycine receptor”
```
69
What is an additional function of glycine?
However, glycine, a ubiquitous part of intermediary metabolism, also serves as a co-agonist for the NMDA glutamate receptor by binding to a novel site on that receptor (which is not responsive to strychnine). Brain levels of glycine may therefore modulate glutamatergic transmission in brain.
70
What are Catecholamine Neurotransmitters?
```
All derived from tyrosine and include:
• Dopamine (DA)
• Norepinephrine (NE)
• Epinephrine (E)
All are utilized by a small number of neurons that are in tightly packed nuclei in the brainstem.
```
Yet, DA and NE neurons give rise to extremely widespread innervation of most regions of the brain and spinal cord.
71
Where are NE and E used/released from?
NE is major transmitter of the sympathetic nervous system, while E is the transmitter released from the adrenal medulla.
72
What are the degrative enzymes of catecholamine nts?
Degradative enzymes: MAO and COMT
73
What kind of receptors are dopamine receptors?
All dopamine receptors are GPCRs:
D1 (D1, D5) D2 (D2, D3, D4)
Coupled to Gs Coupled to Gi
Serves as autoreceptor
74
What are the functions of dopamine receptors?
Nigrostriatal Extrapyramidal motor function
Mesocorticolimbic Key role in regulating emotional behavior (e.g., reward & motivation) & cognition
Arcuate-pituitary Inhibits prolactic secretion from pituitary
75
What are the 3 major pathways of dopamine projections in the brain?
1. Nigrostriatal, from SN to striatum
2. Mesocorticolimbic, from VTA to several limbic and cortical regions
3. arcuate to anterior pituitary (tuberoinfundibular)
76
What are all psychostimulants?
All psychostimulant drugs (cocaine, amphetamine, methylphenidate) promote dopamine function by inhibiting reuptake or stimulating release.
77
What are all antipsychotics?
All antipsychotic drugs are antagonists (or weak partial agonists) at D2 receptors.
78
What is used to treat Parkinson's?
L-DOPA and D2 agonists used to treat Parkinson’s disease.
79
What is the most important noradenergic projection in the brain?
Several brainstem nuclei, the most important of which is the locus ceruleus in pons.
80
What kind of receptors are NE receptors?
All NE receptors are GPCRs
81
What are the 3 kind of NE receptors coupled to?
Beta receptors Alpha 1 receptors Alpha 2 receptors
Coupled to Gs Coupled to Gq Coupled to Gi
Autoreceptor
82
What role does NE play in the brain?
* Essential role in vigilance and attention
* Central control over sympathetic nervous system
* Involved in regulating stress responses and emotional behavior
83
What role does NE play in the autonomic nervous system?
• Most postganglion sympathetic neurons are noradrenergic
84
How do many antidepressants affect NE signalling?
Many antidepressant drugs inhibit NE reuptake and inhibit 5HT reuptake. MAO inhibitors also used as antidepressants.
85
What non-psych meds act on NE receptors?
Many drugs used for treatment of cardiovascular disease and upper respiratory function act on NE receptors.
86
What are Indolamine Neurotransmitters?
Derived from tryptophan and include:
• Serotonin (5HT)
• Melatonin
87
Where does serotonin function?
5HT is utilized by a small number of neurons that are in tightly packed nuclei in the brainstem.
Yet, 5HT neurons give rise to extremely widespread innervation of most regions of the brain and spinal cord.
88
What is the degrative enzyme for indolamine nts?
MAO
89
What is an important serotinergic projection in the brain?
Several brainstem nuclei, the most important of which is the dorsal raphe in midbrain.
90
What are the classes of serotonin receptors and what are they coupled to?
5HT1 receptors
Coupled to Gi autoreceptor
5HT2 receptors
Coupled to Gq
5HT3 receptors
Ligand-gated
5HT4-7 receptor
Coupled to Gs
91
What are the functions of serotonin receptors?
* Involved in regulating stress responses and emotional behavior
* Involved in regulating eating and weight control
92
What do newer antipsychotic drugs do?
Newer antipsychotic drugs block 5HT2A receptors (in addition to D2 receptors)
93
What do hallucinogens do?
while hallucinogens are 5HT2A partial agonists.
94
What do newer anti-migraine drugs (triptans) do?
Newer anti-migraine drugs (triptans) are 5HT1D agonists.
95
Discuss acetlycholine.
1. Derived from choline.
2. ACh is utilized by a small number of neurons that are in tightly packed nuclei in brainstem and forebrain, and by interneurons in striatum.
3. ACh neurons give rise to more focused projections (important one to hippocampus).
4. Degradative enzyme: acetylcholinesterase.
96
Describe the two important cholinergic projection pathways in the brain.
“Basal forebrain” nuclei (medial septal nucleus Ch1 and diagonal band Ch2/3, and nucleus basalis of meynart Ch4) project to hippocampus and are important for cognition.
Brainstem nuclei Ch5-8 (dorsolateral
tegmentum in pons) project widely and are important for sleep.
97
What are the main classes of ACh receptors?
Two main classes of ACh receptors:
Ligand-gated channels GPCRs (“metabotropic receptors”) Nicotinic receptors Muscarinic receptors
Serve as autoreceptor
98
What are the functions of ACh receptors?
* Essential role in cognition
* Involved in regulating sleep-wake cycles
* Modulates striatal function
99
What is the function of ACh receptors in the autonomic nervous system?
• All preganglionic sympathetic and parasympathetic neurons, and most postganglionic parasympathetic neurons, are cholinergic.
100
How does acetylcholine factor into the somatic motor system?
Neuromuscular junction is cholinergic (nicotinic receptors).
101
Which Cranial Nerves Come Out of Which Brainstem Regions?
“2-4-3’s Rule” (slightly simplified)
Ignore CN I, II, and XI, cause they’re weird
CNs III and IV come out of the midbrain (“2”)
CNs V, VI, VII, VIII come out of the pons (“4”)
CNs IX, X, XII come out of the medulla (“3”)
102
What marks the transition from brain stem to spinal cord?
The pyramidal decussation.
103
Draw the circle of willis.
.
104
Describe the path of the fornix.
The fornix loops posteriorly, then anteriorly, passing the splenium of the corpus callosum and then clinging to the septum pellucidum before descending to the mammillary bodies.
105
What is the spatial relationship of the fornix, lateral ventricle, and caudate nucleus?
the fornix is most medial. then lateral ventricle, and caudate nucleus runs on the lateral side of the lateral ventricle.
106
Where are the global pallidus, the putamen, the caudate nucleus, and the thalmus in relation to the internal capsule?
The putamen and globus pallidus are lateral to the internal capsule,
the caudate nucleus and thalamus are medial to it.
107
What are the structures of the midbrain?
Optic tract, occulermotor nerve, substantia nigra, cerebral peduncles, red nucleus, cerebral aqueducts, periaqueductal gray, superior colliculus.
108
What would you find in a crossection of the pons?
Crossing fibers of the pons, pontine nuclei, descending fibers, superior cerebellar peduncles, 4th ventricle, trochlear nerve
109
What would you find in two descending sections of the brainstem?
Descending fibers (pyramids), inferior olivary complex, raphe nuclei, XIIth nerve, Inferior cerebellar peduncle and IVth ventricle.
In the lower section you would still have all of the above except the raphe and now you would have the cranial nerves 9-11.
110
What is gastrulation?
The induction of neural ectoderm from general ectoderm, forming the neural plate.
111
What is neurulation?
The development of the neural tube and neural crests from the neural ectoderm
112
When does the neural tube begin to close?
Neural tube closure begins at ~22 days
Anterior closure = 26 days
Posterior closure = 28 days
113
When is neural tube formation during gestation? (when it can be interrupted)
Neurulation: Neural tube formation 3-4 weeks of gestation
114
Discuss neural tube deffects.
Failure of fusion of neural tube and its mesenchymal coverings (meninges/skull) by the 28th day post conception (4th week)
Most common malformations of the nervous system
Seen in 1/1000 pregnancies
Most common NTDs are anencephaly and myelomeningocele
115
What causes NTDs and what are signs of it?
Associated with low folic acid intake before conception and during pregnancy
Increased alpha-fetoprotein (AFP) in amniotic fluid and serum
Increased AChE in amniotic fluid (because of connection with it and fetal CSF)
116
What is Anencephaly?
Complete failure of anterior neural tube closure results in absence of brain formation
Almost always leads to spontaneous abortion
If born usually die within the first few days but will have brainstem function-suck, gag and can breathe on their own
Increased AFP
Polyhydramnios (no swallowing center in brian)
Associated with maternal diabetes (type 1)
117
What is Encephalocele?
Restricted failure of anterior neural tube closure (around day 26) although less severe forms may occur from later failure of fusion.
Always have meningeal +/- cortical tissue extruding through a bony defect
Protruding tissue may be normal brain or gliotic tissue with little/no function
Depending on size and location usually compatible with life (30% mortality)
Diagnosed prenatally by ultrasound in 80% of cases
Usually surgically repaired unless it is massive and there is severe microcephaly or other lethal anomalies.
118
What is Myelomeningocele?
The meninges and spinal cord herniate through a spinal canal defect. Restricted failure of posterior neural tube closure
Absence of overlying skin, meninges, malformed spinal cord
Impairment in spinal cord and brain
119
What is a Chiari 2 Malformation?
Associated with thoraco-lumbar myelomeningocele
Downward displacement of medulla and tonsils through he foramen magnum
Elongation/thinning of upper medulla/pons.
```
Symptoms:
Brainstem dysfunction
apnea
cyanotic spells
dysphagia
Hydrocephalus
```
If spinal lesion is above the sacral level then almost all will have Chiari 2
120
What are the differences between the two chiari formations?
Type 1: abnormally shaped cerebellar tonsils displaced below the foramen magnum
Type 2: downward displacement of the vermis and tonsils, brainstem malformation with beaked midbrain and spinal myelomeningocele
121
What is Syringomyelia?
Associated with Chiari I malformation (> 3-5 mm celrebellar tonsillar ectopia)
Most common at C8-T1
Cystic enlargement of central canal of spinal cord
Crossing fibers of spinothalamic tract are damaged
Cape-like bilateral loss of pain and temperature sensation in upper extremities
122
Where are the CNS and PNS derived from embryologically?
CNS - neural tube derivative
Brain (cerebrum and brainstem)
Spinal cord
PNS – neural crest derivative
```
Spinal (sensory and motor) nerves
Sensory ganglia
Schwann cells
Pia and arachnoid
Autonomic nervous system
Sympathetic ns
Parasympathetic ns
Enteric ns
```
123
What develops into the spinal cord?
Alar plate, basal plate, and sulcus limitans
124
What develops into the medulla?
Alar plate, basal plate, sulcus limitans,
| ependymal roof – tela choroidia
125
What fibers do the Basal and Alar plates give rise to?
Basal: GSE, GVE, SVA Save Geese Give Basic (meat)
Alar: GVA/SVA, GSA, SSA Save the Gas, Gave the Sass.
126
What's the difference between the 3 and 5 vessicle stage?
The Prosencephalon gives rise to the Telencephalon
and Diencephalon.
The Mesencephalon stays as the Mesencephalon
The Rhombencephalon gives rise to the Metencephalon
and the Myelencephalon.
127
What are the 3 main flexures in neural development?
(Mesen)cephalic
Pontine
Cervical
128
When does Prosencephalic development occurduring gestation?
5-6 Weeks
129
What is Holoprosencephaly?
Failure of left and right hemispheres to seprate
Mutations in Shh pathway
Moderate = cleft lip/palate
Severe = cyclopia
Neurologic dysfunction inversely correlates with degree of hemispheric separation
Normal facial appearance to dramatically altered
Craniofacial anomalies accompany HPE in 80% of patients.
130
When does Cortical formation happen during gestation?
8-24 weeks
131
What is Focal Cortical Dysplasia?
Neurons exhibit immature or glial features.
Cortex contains large dysplastic neurons that are not organized into typical layers and underlying white matter is hypomyelinated
Wider than normal gyri (pachygyria)
Blurred gray/white junction
Often have epilepsy requiring surgery
This is a disorder of differentiation/maturation.
132
What is Lissencephaly?
Lissencephaly
Type 1 (classical) arrest of neuronal migration
Type 2 (cobblestone) over migration
Paucity of normal gyri/sulci so get a “smooth brain”
This is a disorder of migration.
133
Describe classical Lissencephaly.
Have a brain that has agyria and pachygryia (reduced number of abnormally large gyri)
Agyria: diminished white matter, shallow or absent sylvian fissures-more disorganized neurons
Pachygryia: reduced number of abnormally broad and flat gyri
Pathophysiology:
disruption of platelet-activating factor which interacts with microtubules
Etiology:
Genetic: double cortin on x chromosome
Males: severe classic lissencephaly
Females: less severe with “double cortex”
Clinically:
Depends on amount of agyria vs.pachygyria
Greater gyral simplification = greater impairment
Epilepsy (commonly infantile spasms)
Developmental delay
Spastic quadriperisis
Other parts of the brain (cerebellum) and other parts of the body can be affected.
134
What is Dandy-Walker?
Associated with hydrocephalus and spina bifida
Constitute 3-4 % of congenital hydrocephalus
Etiology: sporadic or isoretinoid during pregnancy
Consists of:
Hypoplasia or absence of vermis
4th ventricle transformed into a large cystic cavity with thin roof lined with ependyma
failure of Luschka and Magendie to open
Posterior fossa is large and lateral sinuses and torcula are elevated
135
Describe cleft lip/palate
Most common craniofacial malformation identified in newborn
Equally divided: 1/3 have combined cleft lip and palate, 1/3 isolated cleft lip and 1/3 have isolated cleft palate
Both or just cleft lip:
2/3 are nonsyndromic
Ethnic variance-highest rate in Asians/Native Americans and lowest in American blacks
More common in males
Just cleft palate: ½ are nonsyndromic
No variance with ethnicity
More common in females
136
What can cause a clefy lip/palate?
Genetic:
genetically complex event
Up to 20 genes thought to interact to result in facial clefting
Drugs:
Phenytoin, valproic acid, topiramate, methotrexate
Cigarettes
Alcohol (esp. with weekly binge drinking)
Environmental:
Folate deficiency
Maternal obesity
137
What causes cleft lip/palate embryologically?
Cleft lip +/- palate
Failure of one or all of the lateral nasal, median nasal and maxillary mesodermal processes merge.
Can produce unilateral/bilateral or median lip clefting
Cleft palate (isolated) occurs when there is
Lack of fusion of palatal shelves (separate process from lip closure occurs later)
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What is cerebral palsy?
Permanent disorder of movement and posture causing activity limitation
Attributed to non-progressive disturbance that occurred in the fetal or infant brain
Often but no always accompanied by:
Disturbance of sensation, perception, cognition, communication, behavior Epilepsy
Secondary musculoskeletal problems may develop
Worldwide incidence is 2-4/1000 live births
In US 10,000 babies born with CP annually
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What is the prenatal etiology for CP?
Causes:
Hemorrhagic or ischemic stroke
Acquired/Hereditary thrombophilia or placental issues
CNS malformations
Periventricular leukomalacia
periventricular white matter focal necrosis and cyst formation
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Risk factors:
>2 previous abortions
Maternal MR
Bleeding during pregnancy
Preeclampsia
SGA
Placental infection
Multiple births
Maternal hypothyroidism
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140
What is the perinatal etiology for CP?
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Causes:
Asphyxia
Hyperbilirubinemia
CNS infection
Hemorrhage
Intraventricular hemorrhage
Vascular malformation/tumor
Hydrocephalus
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Risk factors:
Prematurity
Low birth weight
Placenta previa or abruption
PROM
Meconium
Nuchal cord
Decreased fetal heart rate
Breech
APGAR <5 at 5 minutes
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