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During development, ................ has an important role in defining neuronal number
What is Acute neuronal injury (“red neurons”) ?
changes that accompany acute CNS hypoxia/ischemia or other acute insults and reflect cell death, either necrosis or apoptosis
What are the features of red neurons?
- “Red neurons” are evident with hematoxylin and eosin (H&E) preparations at about 12 to 24 hours after an irreversible hypoxic/ischemic insult.
- Shrinkage of the cell body
- Disappearance of the nucleolus
- Loss of Nissl substance
- Intense eosinophilia of the cytoplasm.
What is Subacute and chronic neuronal injury (“degeneration”)?
neuronal death occurring as a result of a progressive disease process of some duration, as is seen in certain slowly evolving neurologic diseases such as amyotrophic lateral sclerosis (ALS).
What is the characteristic histological features of degeneration?
- Cell loss, often selectively involving functionally related groups of neurons, and reactive gliosis.
- When the process is at an early stage, the cell loss is difficult to detect; the associated reactive glial changes are often the best indicator of the pathologic process
- Mostly Apoptosis
Neuronal ................ is seen when there is a destructive process that interrupts the majority of the afferent input to a group of neurons.
What is axonal reaction?
Axonal reaction refers to the reaction within the cell body that attends regeneration of the axon
What is responsible for axonal reaction?
Where is the axonal reaction best seen?
it is best seen in anterior horn cells of the spinal cord when motor axons are cut or seriously damaged
What are the histological features of axonal reaction?
- There is increased protein synthesis associated with axonal sprouting.
- Enlargement and rounding up of the cell body
- Peripheral displacement of the nucleus
- Enlargement of the nucleolus
- Dispersion of Nissl substance from the center to the periphery of the cell (central chromatolysis).
Neuronal inclusions may occur as a manifestation of aging, when there are ......................................................
intracytoplasmic accumulations of complex lipids (lipofuscin), proteins, or carbohydrates.
What are the viral inclusions in CNS infection?
- IN--> Cowdry A in HSV
- IC---> Negri
- IC +IN--> CMV
What are the inclusions in neurodegeneratvie diseases?
- NFT in AD
- LB in PD
- Both intracytoplasmic
Abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil is seen in ...................
What are the features of intracellular aggregates in proteinopathies (degenerative brain diseases)?
- Resistant to degradation
- contain proteins with altered conformation, and may result from mutations that affect protein folding, ubiquitination, and intracellular trafficking
What is the cause of injury in CNS proteinopathies?
There is increasing evidence in many of these diseases that the visible aggregates are not the basis of cellular injuries; rather, small multimers of the proteins (oligomers) are the critical mediators of the damage.
Acute ischemic injury causes ............. of neurons
What are the features of astrocytes?
- Star-shaped appearance
- Multipolar, branching cytoplasmic processes that emanate from the cell body and contain the glial fibrillary acidic protein (GFAP), a cell type–specific intermediate filament
- Astrocytes act as metabolic buffers and detoxifiers within the brain.
- Through the foot processes, which surround capillaries or extend to the subpial and subependymal zones, they contribute to barrier functions controlling the flow of macromolecules between the blood, the cerebrospinal fluid (CSF), and the brain.
How can astrocytes be distinguished in an specimen?
What are the main cell responsible for gliosis?
What are the features of gliosis?
- Gliosis (or astrogliosis) is the most important histopathologic indicator of CNS injury, regardless of etiology, and is characterized by both hypertrophy and hyperplasia.
- In this reaction, the nuclei of astrocytes, which are typically round to oval (10 μm wide) with evenly dispersed, pale chromatin, enlarge, become vesicular, and develop prominent nucleoli.
- The previously scant cytoplasm expands to a bright pink, somewhat irregular swath around an eccentric nucleus, from which emerge numerous stout, ramifying processes; these cells are called gemistocytic astrocytes.
..................... is the most important histopathologic indicator of CNS injury
Gliosis (or astrogliosis)
What are the functions of astrocytes?
- Recycling of GABA and glutamate
- Synthesis of glutamine from glutamate that is then releseased to EC space and is taken by neurons
- Ion Balance
- Glycogen storage (only glucose storage in the CNS)
What is the reaction of astrocytes to direct injury?
- cytoplasmic swelling
- Particularly occurring in the setting of ATP-depletion
What are Alzheimer type II astrocytes?
- is a gray-matter cell with a large (two to three times normal) nucleus, pale-staining central chromatin, an intranuclear glycogen droplet, and a prominent nuclear membrane and nucleolus
- Seen in hyperammonemia
Which cells are responsible for scar in the CNS?
Rosenthal fibers are ................
Rosenthal fibers are thick, elongated, brightly eosinophilic, somewhat irregular structures that occur within astrocytic processes, and contain two heat-shock proteins (αB-crystallin and hsp27) as well as ubiquitin.
Rosenthal fibers are seen in ...................
- 1)Rosenthal fibers are typically found in regions of long-standing gliosis2)pilocytic astrocytoma. 3) In Alexander disease, a leukodystrophy associated with a mutations in the gene encoding GFAP
What is corpora amylacea , or polyglucosan bodies?
- Round, faintly basophilic, (PAS)–positive, concentrically lamellated located wherever there are astrocytic end processes, especially in the subpial and perivascular zones.
- Consist of GAG, HSP, and ubiquitin.
- Advancing age (thought to represent a degenerative change in the astrocyte) The Lafora bodies that are seen in the cytoplasm of neurons (as well as hepatocytes,...) in myoclonic epilepsy is similar
True or false
oligodendrocytes and ependyma do not participate in the active response to CNS injury
Each oligodendrocyte myelinates ..........................
numerous internodes on multiple axons
Injury or apoptosis of oligodendroglial cells is a feature of ........................
acquired demyelinating disorders and leukodystrophies.
Oligodendroglial nuclear and cytoplasmic inclusions are seen in ............. and ........... respectively
PML, MSA (alpha synuclein)
What are ependymal granulations?
When there is inflammation or marked dilation of the ventricular system, disruption of the ependymal lining is paired with proliferation of subependymal astrocytes to produce small irregularities on the ventricular surfaces (ependymal granulations)
What viral infection can damage ependymal cells?
What are the markers of microglia?
CR3 and CD68
What are the reactions of microglia to injury?
- (1) proliferating
- (2) developing elongated nuclei (rod cells), as in neurosyphilis
- (3) forming aggregates about small foci of tissue necrosis (microglial nodules)
- (4) congregating around cell bodies of dying neurons(neuronophagia).
What are the features of IIH?
- Obese women
- daily occurrence, unusual severity, and a throbbing quality
- Papilledema is usually bilateral and symmetric (related to visual loss)
- transient visual obscurations, pulsatile tinnitus, and diplopia
- restricted visual fields and uni- or bilateral abducens palsy.
What are the most important association of IIH?
- Obese women
- Retinoic acid
What are the mc MRI finding in IIH?
Flattening of the posterior sclera>Empty sella
How is IIH diagnosed?
LP CSF pressure of greater than 250 mmH2O
What are the features of NPH?
1) Idiopathic or secondary due to SAH, or meningitis followed by impaired cerebrospinal fluid (CSF) resorption
2) cognitive impairment (frontal, subcortical), gait disturbance (wide based, foot stuck on the floor, supplementary motor), and urinary incontinence (urgency followed by lack of concern, frontal)
3) ventriculomegaly out of proportion to sulcal enlargement and no evidence of CSF flow obstruction
What are the mcc of hydrocephalus?
- Obstructive -->MCC
- Communicating hydrocephalus occurs when full communication occurs between the ventricles and subarachnoid space. It is caused by overproduction of CSF (rarely), defective absorption of CSF (most often), or venous drainage insufficiency (occasionally).
- he most common causes of congenital hydrocephalus are obstruction of the cerebral aqueduct flow, Arnold-Chiari malformation or Dandy–Walker malformation.
What are the ventricular change in obstructive hydrocephalus?
- Dilatation of the ventricular system occurs proximal to the obstruction. The ventricle just proximal to the obstruction usually dilates most prominently. As examples:
- Obstruction of the aqueduct of Sylvius (aqueductal stenosis) causes dilation of the lateral and third ventricles, while the size of the fourth ventricle remains relatively normal. This is a very common cause of hydrocephalus in infants and children.
- Obstruction at the body of the lateral ventricle causes dilation of the distal temporal horn and atrium.
- Obstruction of one foramen of Monro causes dilatation of the lateral ventricle on that side
What are the types of cerebral edema?
What is the pathophysiology of vasogenic edema?
- Vasogenic edema is caused by blood-brain barrier disruption and increased vascular permeability, allowing fluid to shift from the intravascular compartment to the intercellular spaces of the brain. The paucity of lymphatics greatly impairs the resorption of excess extracellular fluid.
- Vasogenic edema may be either localized (e.g., adjacent to inflammation or neoplasms) or generalized
What is cytotoxic edema?
Cytotoxic edema is an increase in intracellular fluid secondary to neuronal, glial, or endothelial cell membrane injury, as might be encountered in someone with a generalized hypoxic/ischemic insult or with metabolic damage.
conditions associated with generalized edema are often of ................. type
Both cytotoxic and vasogenic
Interstitial edema (hydrocephalic edema) occurs .......................
especially around the lateral ventricles when an increase in intravascular pressure causes an abnormal flow of fluid from the intraventricular CSF across the ependymal lining to the periventricular white matter
What are the gross changes in brain generalized edema?
In generalized edema, the gyri are flattened, the intervening sulci are narrowed, and the ventricular cavities are compressed
CSF enters the ............... through the foramina of Luschka and Magendie
Cisterna magna at the base of the brain stem
What is the difference in hydrocephalus in infancy with adulthood?
- When hydrocephalus develops in infancy before closure of the cranial sutures, there is enlargement of the head, manifested by an increase in head circumference.
- Hydrocephalus developing after this period, in contrast, is associated with expansion of the ventricles and increased intracranial pressure, without a change in head circumference
hydrocephalus ex vacuo refers to .....................
dilation of the ventricular system with a compensatory increase in CSF volume secondary to a loss of brain parenchyma
When does the pressure within the skull increase?
When the volume of the brain increases beyond the limit permitted by compression of veins and displacement of CSF, the pressure within the skull will increase
What are the features of subfalcine herniation?
- Subfalcine (cingulate) herniation occurs when unilateral or asymmetric expansion of a cerebral hemisphere displaces the cingulate gyrus under the falx cerebri.
- This may lead to compression of branches of the ACA.
What are the clinical features associated with transtentorial, uncal, or mesial temporal herniation?
- Compression of III at the side of the herniation---> pupillary dilation+ eye down and out ipsilaterallyCompression of PCA--> lesion of primary visual cortex ipsilaterally (homonymous hemianopsia of contralateral field)
- Compression of contralateral cerebral peduncle (if large)---> ipsilateral hemiparesis
- Duret hemorrhage (midbrain and pons)
Transtentorial (uncinate, mesial temporal) herniation occurs when .......................
the medial aspect of the temporal lobe is compressed against the free margin of the tentorium
When the extent of uncal herniation is large enough ................. may be compressed, resulting in hemiparesis ipsilateral to the side of the herniation; the change in the peduncle in this setting is known as ................
the contralateral cerebral peduncle/ Kernohan's notch
What is Duret hemorrhage?
- Progression of transtentorial herniation is often accompanied by hemorrhagic lesions in the midbrain and pons, termed secondary brainstem, or Duret, hemorrhages .
- These linear or flame-shaped lesions usually occur in the midline and paramedian regions and are believed to be due to distortion or tearing of penetrating veins and arteries supplying the upper brainstem.
What are the features of tonsillar herniation?
- Tonsillar herniation refers to displacement of the cerebellar tonsils through the foramen magnum.
- This pattern of herniation is life-threatening because it causes brainstem compression and compromises vital respiratory and cardiac centers in the medulla oblongata