Lecture 14-16: CNS Flashcards
1
Q
Recall the parts of the nervous system.
A
2
Q
Describe the brain.
A
3
Q
Recall the topography of the brain.
A
4
Q
What is the main function of the spinal column?
A
5
Q
Recall the various CNS injuries.
A
6
Q
Recall the protecting structures of the CNS.
A
- Skull and vertebral column
- Meninges
- Cerebral Spinal Fluid (CSF)
- Blood-brain barrier (BBB)
- Glia cells
7
Q
Describe the CSF.
A
8
Q
Describe the blood-brain barrier
A
9
Q
What are pericytes?
A
10
Q
Recall the function of the blood-brain barrier.
A
11
Q
Recall grey and white matter.
A
12
Q
Describe neurons.
A
13
Q
Recall the types of neurons.
A
14
Q
Recall neuronal morphology.
A
15
Q
Recall arrangement of neurons.
A
16
Q
Recall the neuronal layer arrangement.
A
17
Q
Describe glial cells.
A
18
Q
Describe oligodendrocytes.
A
Synthesise myelin in the CNS
19
Q
Recall information regarding myelin formation.
A
20
Q
Recall the function of myelin.
A
21
Q
Describe astrocytes.
A
22
Q
Recall astrocyte organization.
A
23
Q
Recall the features of astrocytes in adult brain.
A
24
Q
Recall the CNS function that involves astrocytes.
A
25
Describe microglia.
26
Recall the function of microglia.
27
Recall the 4 different phenotypes of microglia.
28
Recall acute neuronal injury.
Pyknosis is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
“Red neurons” are evident by about 12 to 24 hours after an irreversible hypoxic/ ischemic insult.
29
Recall subacute and chronic neuronal injury.
Subacute and chronic neuronal injury (“degeneration”) refers to neuronal death occurring as a result of a progressive disease of some duration
At an early stage, the cell loss is difficult to detect; the associated reactive glial changes are often the best indicator of neuronal injury. For many of these diseases, there is evidence that cell loss occurs via apoptotic death.
30
Recall transsynaptic degeneration.
31
Recall axonal reaction.
Axonal reaction is a change observed in the cell body during regeneration of the axon
There is increased protein synthesis associated with axonal sprouting. This is reflected in enlargement and rounding up of the cell body, peripheral displacement of the nucleus, enlargement of the nucleolus, and dispersion of Nissl substance from the center to the periphery of the cell (central chromatolysis).
32
Recall neuronal and cytoplasmic inclusion
Neuronal inclusions may occur as a manifestation of aging when there are intracytoplasmic accumulations of complex lipids (lipofuscin), proteins, or carbohydrates.
33
Recall injury potential of oligodendrocytes.
34
When directly injured as result of ischaemia, toxicity or acute inflammation cytoplasmic swelling occurs as result of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
35
Recall the response of astrocytes to injury,
36
Hypertrophy and hyperplasia of astrocytes are detected with \_\_\_\_\_\_\_.
GFAP
37
Recall the two distinct phenotypes of reactive astrocytes.
38
Recall the response of microglia in response to injury.
39
Define TBI
Traumatic Brain Injury refers to an external force that exceeds the protective capacity of the brain. It involves blows, bumps, projectiles, or blast.
Leads to mechanical injury: compression, shearing, tearing, and stretching of brain tissue. It would affect neurons, axons, glial cells, and blood vessels. Effects could be temporary or lifetime.
40
Recall the outcomes of TBI.
41
Describe brain parenchymal injury resulting from trauma.
A contusion is analogous to the familiar bruise caused by blunt trauma, while a laceration is an injury caused by penetration of an object and tearing of tissue.
A person who suffers a blow to the head may develop a contusion at the point of contact (a coup injury) or a contusion on the brain surface diametrically opposite to it (a contrecoup injury).
42
Describe vascular injury due to brain trauma.
43
Differ between epidural and subdural hematoma
44
Describe cerebrovascular disease.
Cerebrovascular disease—injury to the brain as a consequence of altered blood flow—can be grouped into ischemic and hemorrhagic etiologies. “Stroke” is the clinical designation that applies to all these conditions, particularly when symptoms begin acutely.
45
Recall global cerebral ischaemia
There is a hierarchy of sensitivity among CNS cells: neurons are the most sensitive, although glial cells (oligodendrocytes and astrocytes) are also vulnerable.
The most sensitive neurons in the brain are in the pyramidal cell layer of the hippocampus (especially area CA1, also referred to as Sommer sector), cerebellar Purkinje cells and pyramidal neurons in the cerebral cortex.
Border zone (“watershed”) infarcts occur in the regions of the brain or spinal cord that lie at the most distal reaches of the arterial blood supply, the border zones between arterial territories.
46
Describe focal cerebral ischaemia
Focal cerebral ischemia follows reduction or cessation of blood flow to a localized area of the brain due to arterial occlusion or hypoperfusion.
The size, location, and shape of the infarct and the extent of tissue damage that results are influenced by the duration of the ischemia and the adequacy of collateral flow.
Occlusive vascular disease of severity sufficient to lead to cerebral infarction may be due to embolization from a distant source, in situ thrombosis, or various forms of vasculitides
47
Describe intraparenchymal hemorrhage
Rupture of a small intraparenchymal vessel can result in a hemorrhage within the brain, often associated with sudden onset of neurologic symptoms (stroke).
Hypertension is the risk factor most commonly associated with deep brain parenchymal hemorrhages
Acute hemorrhages, independent of etiology, are characterized by extravasation of blood with compression of the adjacent parenchyma
48
Recall the cause and effect of infection in the CNS.
49
Describe meningitis and its pathogenesis in CNS.
Meningitis is an inflammatory process of the leptomeninges and CSF within the subarachnoid space, usually caused by an infection.
50
Describe HIV encephalitis
Viral encephalitis is a parenchymal infection of the brain almost invariably associated with meningeal inflammation (meningoencephalitis) and sometimes with simultaneous involvement of the spinal cord (encephalomyelitis).
HIV encephalitis is a chronic inflammatory reaction associated with widely distributed microglial nodules, often containing macrophage-derived multinucleated giant cells; foci of tissue necrosis and reactive gliosis are sometimes seen together with these lesions.
A wide range of possible mechanisms for neuronal dysfunction and injury in this setting have been proposed, including the **actions of inflammatory cytokines and a cascade of toxic effects of HIV-derived proteins**; in all probability, both have contributory roles in the pathogenesis of brain injury
51
Recall demyelinating diseases
Demyelinating diseases of the CNS have acquired conditions characterized by preferential damage to myelin with relative preservation of axons.
Several pathologic processes can cause loss of myelin. These include immunemediated destruction of myelin, as in multiple sclerosis, and infections. In progressive multifocal leukoencephalopathy, JC virus infection of oligodendrocytes results in loss of myelin (described earlier). In addition, inherited disorders may affect synthesis or turnover of myelin components; these are termed leukodystrophies and are discussed with metabolic disorders.
52
Describe multiple sclerosis.
Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits, separated in time, attributable to white matter lesions that are separated in space.
The disease may become clinically apparent at any age, although onset in childhood or after age 50 years is relatively rare.
53
Recall the pathogenesis of MS.
The lesions of MS are caused by an autoimmune response directed against components of the myelin sheath. As in other autoimmune disorders, the pathogenesis of this disease involves both genetic and environmental factors
MS is a white matter disease that is best appreciated in sections of the brain and spinal cord. In the fresh state, the lesions are firmer than the surrounding white matter (sclerosis) and appear as well-circumscribed, somewhat depressed, glassy, grey-tan, irregularly shaped plaques
54
Recall the histology of MS.
55
Recall the overview of genetic metabolic disease.
Disruption of metabolic processes in neurons and glia, particularly those involved in synthetic or degradation pathways that are specific to the nervous system, results in diseases that typically present early in life and progress.
Types: Neuronal storage diseases, Leukodystrophies, and Mitochondrial encephalomyopathies
56
Recall neuronal storage disease.
Neuronal storage diseases are predominantly autosomal recessive disorders caused by the deficiency of a specific enzyme involved in the catabolism of sphingolipids (including the gangliosides), mucopolysaccharides, or mucolipids. They are often characterized by the accumulation of the missing enzyme’s substrate within the lysosomes of neurons, leading to neuronal death. Cortical neuronal involvement leads to loss of cognitive function and may also cause seizures.
57
What is leukodystrophies?
Leukodystrophies are mostly autosomal recessive disorders caused by mutations in genes encoding enzymes involved in myelin synthesis or catabolism. Some of these disorders involve lysosomal enzymes, while others affect peroxisomal enzymes. There is typically diffuse involvement of white matter leading to deterioration in motor skills, spasticity, hypotonia, or ataxia.
58
Recall lysosomal storage disease (Tay Sachs)
An example of neuronal storage disease
59
Recall the types of tumours in the CNS.
60
Recall the characteristic of degenerative disorders of the CNS.
* Diseases of grey matter
* Progressive loss of neurons
* Selective targeting of neuronal functional groups (event if they are not immediately adjacent)
* Symptomatic/anatomic: based on the anatomic regions of the CNS that are primarily affected
* Alzheimer's
* Parkinson's
* Pick's
* Pathologic: based on the types of inclusions or abnormal structures observed
* Tauopathies
* Prion disease
61
Recall the Relationship Between Proteins and Neurodegenerative Diseases
62
Describe Parkinson's Disease.
PD is a neurodegenerative disease marked by a prominent hypokinetic movement disorder that is caused by loss of dopaminergic neurons from the substantia nigra.
Autosomal dominant PD encodes α-synuclein, an abundant lipid-binding protein normally associated with synapses. This protein was then demonstrated to be a major component of the Lewy body, which is the diagnostic hallmark of PD.
Mutations in the gene encoding LRRK2 (leucinerich repeat kinase 2) are a more common cause of autosomal dominant PD
63
Recall the overview of toxic and acquired metabolic diseases.
64
Mention the challenges to diagnosing or treating CNS injuries.
65
Mention the preferred characteristics of CNS diagnosis procedures.
66
Recall diagnostic procedures for various CNS diseases.
* specific PET imaging for AD
* detection of blood biomarkers for AD
* use of biomarkers for CJD
* CSF 14-3-3 protein in CJD
* 85% sensitivity
* Low specificity
* Note: In medical diagnosis, test sensitivity is the ability of a test to correctly identify those with the disease (true positive rate), whereas test specificity is the ability of the test to correctly identify those without the disease (true negative rate).
67
Mention the desired treatment characteristic for CNS diseases
68
Describe neurogenesis.
69
Describe neural progenitor cells
70
Recall the potential for repair of brain cells.
71
Recall NSC treatment for MPTP-lesion
72
Recall secondary cell death causes.
73
Recall mitochondrial dysfunction.
74
Recall oxidative stress.
75
Recall excitotoxicity.
76
Recall BBB dysfunction.
77
Recall the overview of inflammation response in the brain.
78
Leukocyte penetration into the CNS is \_\_\_\_\_\_\_\_\_\_\_. Under homeostatic conditions, leukocyte trafficking is relatively ______ and the cells rarely enter the \_\_\_\_\_\_\_\_\_.
79
Recall the effects of inflammation in the CNS.
80
Recall the beneficial and detrimental outcomes of neuroinflammation.
81
Recall the role of M1/2 microglia and A1/2 astrocytes.
82
Recall the timeline fo neuroinflammation.
83
Mention the two consequences of neuroinflammation.
* raised intracranial pressure
* chronic traumatic encephalopathy
84
Describe the effects of raised intracranial pressure.
Consequences:
* Local hypoxia and ischaemia
* Secondary hemorrhage
* Herniation
85
Mention the types of intracranial pressure herniation.
86
Describe chronic traumatic encephalopathy
87
Removal of excess CSF in the CNS occurs through \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
CSF returns to the vascular system by entering the dural venous sinuses via arachnoid granulations. These are outpouchings of the arachnoid mater into the venous sinuses around the brain, with valves to ensure one-way drainage.
88
What are Nissl substance?
Nissl body is a large granular body found in neurons. These granules are of rough endoplasmic reticulum (RER) with rosettes of free ribosomes and are the site of protein synthesis
The functions of Nissl bodies is thought to be the same as that of the rest of the ER and the Golgi apparatus: the manufacture and release of proteins and amino acids.
89
Describe the appearance of astrocytes.
These cells have multipolar, branching cytoplasmic processes that emanate from the cell body and contain glial fibrillary acidic protein (GFAP), a cell typespecific intermediate filament
90
What is reactive gliosis?
Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, microglia, and oligodendrocytes. In its most extreme form, the proliferation associated with gliosis leads to the formation of a glial scar.
91
Recall the features of major neurodegenerative diseases.
92
Idiopathic Parkinson's Disease can be caused by toxic exposure to \_\_\_\_\_\_\_\_\_.
An acute parkinsonian syndrome and destruction
of neurons in the substantial, nigra follows exposure to MPTP, discovered as a contaminant in illicitly synthesized batches of the opioid meperidine. This toxin has been used to generate animal models of PD that are being exploited to test new therapies.
93
What is the herniation and its cause?
A herniation is the displacement of brain tissue past rigid dural folds (the falx and tentorium) or through openings in the skull because of increased intracranial pressure.
As the volume of the brain increases, CSF is displaced and the vasculature is compressed, leading to increased pressure within the cranial cavity. When the increase is beyond the limit permitted by compression of veins and displacement of CSF, tissue herniates between compartments across the pressure gradient
