Proliferation of the lining of the neural tube results in the establishment of ________________.
neuronal and glial stem cell populations
Due to the complexity of the ____________ derivatives, the greatest proliferative and migrational activity is in the ___________; this creates significant potential for developmental defects.
prosencephalic; rostral neural tube
Neuroblasts arise from stem cells at the ____________ and migrate along __________ toward the ______ surface.
ventricular surface; radial glia; pial
Neuronal cell adhesion molecule (NCAM) and nerve growth factor are factors produced by ___________ that mediate the process of neuroblast proliferation and migration.
What are repercussions of failure of development of the diencephalon?
no optic nerve and no retina or lens
Development of the brain is complete at birth with the exception of ____________; the degree of development determines...
cerebellum; whether the animal is ambulatory at birth or not.
Period of neuronal maturation leads to ___________ of structures.
Defect characterized by abnormal tissue organization (dysplasia), reduction in mass (hypoplasia), or total lack of formation (aplasia).
Defect that may not initially evident upon gross or histologic evaluation, but clinical abnormalities may be present.
________________ represent a change that is present at birth, typical of __________ malformations.
Congenital structural defects; cerebral
Cerebellar defects can be... (2)
congenital or arise in postnatal period (due to its delayed maturation).
Defect determined by a particular genotype.
When do heritable defects become evident?
at birth (congenital) or in the postnatal period
__________ defects tend to be more unique in their expression than for __________ defects.
Acquired defects occur due to exposure to ______________.
Radiomimetic agents destroy ____________; therefore, morphologic expression may be ____________.
rapidly dividing cells; similar for diverse agents
4 types of radiomimetic agents.
viruses, toxins, radiation, Cu deficiency
Describe the continuum that manifests as absence of tissue.
hypoplasia <--> segmental aplasia <--> aplasia
Determinants of tissue alteration. (2)
magnitude of insult, timing of insult
Earlier insults result in...
more severe abnormalities.
Abnormalities of neural tube closure.
CNS tisues orchestrate the development of the ____________ of the brain and spinal cord; therefore, dysraphic states are accompanied by defects in ______________, known as __________.
bony encasement; cranial vault/vertebrae; schisis
4 examples of myelodysplasia.
duplication/displacement of ventral fissue, misplaces grey matter, hydromyelia, syringomyelia
Dilation of the central canal.
Formation of blind-ended pouches that extend from the central canal and are not lined by ependymal cells.
Secondary defect in the vertebral arches.
With spina bifida, the functional defect is inferred by abnormal induction of the _____________; the ____________ may be lacking/hypoplastic, reulting in increased vertebral laxity and causing _____________.
Lack of fusion of the vertebral arches, often accompanied by a dermal sinus/tract that communicates with the central canal and containing CSF.
occult spina bifida
Disorder in which CNS structures protrude through the defect in the vertebral arch.
cystic spina bifida
Cystic spina bifida, meningocoele is when...
only the meninges protrude.
Cystic spina bifida, meningomyelocele, is when...
meninges and spinal cord protrude.
Dynamic cord compression results from ___________; ____________ is generally the most severe sequel.
vertebral laxity; Wallerian degeneration
_____________ may result from CNS invasion by bacteria through dermal sinuses that accompany spina bifida.
Amorphous mass of dysplastic cerebral tissue overlies the hindbrain, and eyes are absent.
How is anencephaly associateed with cranioschisis?
cranioschisis- cranium fails to close--> brain is exposed to aminos--> brain degenerates--> anencephaly
Partial aplasia/hypoplasia of the brain.
Disorder that results from an insult that affects a small number of cells over a wide distribution, resulting in subtle reductions in cerebral mass.
3 types of cerebral hypoplasia.
polymicrogyria (increased # of small gyri), pachygyria (decreased # of thicker gyri), lissencephaly (lack of gyri)
Lissencephaly is normal in __________.
Cavitating lesions resulting from pannecrosis usually occur as a result of ___________.
Extensive lesion resulting from complete destruction of the periventriculat germinal zone of the telencephalon.
Mild, multifocal insult resulting in cavities within the neocortex that may communicate with the subarachnoid space or ventricular system.
What is an example of an insult that causes cavitating lesions due to failure of support axons?
Cu deficienccy in small ruminants and pigs
With Cu deficiency in small ruminants, there is an inability of neurons to develop or maintain ______________, and possibly death of ____________, resulting in __(2)__.
axonal processes; death of cerebral cortical neurons; porencephaly or hydranencephaly
Cu-dependent enzyme necessary for phospholipid synthesis; thus, Cu deficiency causes decreased phospholipid production and compromised myelination.
cytochrome c oxidase
Cu-dependent enzyme that confers protection against oxygen radicals;; important b/c superoxide anion generation is increased during neuronal differentiation.
Cu deficiency during the first weeks of life leads to... (2)
enzootic ataxia, anemia
Diffuse symmetric reduction of CNS myelin sheaths and a decrease in oligodendrocytes.
Myelin formation begins in the ___________ of gestation and proceeds into _________; therfore, earaly onset injuries primarily affect the __________, whereas later onset injuries are most extensive in the ___________.
middle; postnatal life; brain; spinal cord
_________ myelin is unaffected in heritable forms of dys/hypomylinogenesis.
PNS (b/c schwann cells are not affected)
Describe embryogenesis of the cerebellum.
neural tube closure--> neuroblast proliferation into the alar plate--> dorsal neuroblast migration from the alar plate to form the rhombic lip
Central migration/proliferation of neuroblasts of the cerebellum forms the... (3)
roof of the 4th ventricle, cerebellar roof nuclei, and Purkinje cells.
Outer migration and proliferation of neuroblasts of the cerebellum forms the... (2)
external granular layer, internal granular layer
The protracted development of the cerebellum leads to...
prolonged susceptibility to mitolytic insults.
Insults to cerebellar neuroblasts can lead to... (2)
lack of rhombic lip formation, laminar hypoplasia
Lack of rhombic lip formation can result in... (2)
agenesis (complete aplasia), segmental aplasia
Laminar hypoplasia leads to loss of the _____________ and subsequently loss of _____________; _____________ is also evident as a dysplastic change.
external granular layer; internal granular layer; mixing of Purkinje cells and surviving granular cells
Viral agents causing cerebellar defects. (2)
parvovirus (panleuk in cats), BVDv
Parvovirus infection in utero or early post-natal period leads to ___________.
BVDv infection at __________ leads to fetal death; at _________, leads to microphthalmia/cerebral defects.
<100 days; 100-170 days
Defects in specific lysosomal enzymes, resulting in the accumulation of the substrate of that defective enzyme.
lysosomal storage disease
Lysosomal storage disease is generally the result of ______________, but ____________ is also a possibility.
hereditary defect in enzyme structure; enzyme inhibitors may be acquired
Describe defects associated with lysosomal storage disease.
defects is generalized, with accumulations of enzyme substrate found in phagocytic cells of the spleen, liver, bone marrow, and lymph nodes
With lipidosis, a _____________ disease, accumulation is predominantly within _________.
lysosomal storage; neurons
Describe the diagnosis of lysosomal storage disease. (3)
immunohistochemistry, biochemical characterization of fibroblast primary cultures, measurement of enzyme activity with and without inhibitor
Lysosomal storage disease can cause __________.
With galactocerebrosidosis, a _____________ disease, accumulation is...
lysosomal storage; NOT primarily in neurons.
Galactocerebroside is primarily a _________ component; thus, galaltocerebrosidosis is a disease of ____________, and the predominant accumulation is in ___________, which for _________.
myelin; oligodendroglia; microglia; gitter cells
Glycoproteinosis looks similar to ___________; __________ is more common.
Lysosomal storage disease characterized by accumulation of an autoflourescent lipopigment; more of a lipid transport problem than a storage problem.
An increase in the CSF volume in the brain, reflecting an imbalance in the rates of production vs resorption.
2 types of hydrocephalus.
communicating hydrocephalus (less common b/c don't live long enough to develop), internal (obstructive) hydroephalus
Physical alteration of the arachnoid granulations such that CSF resorption into the venous circulation occurs at a slow rate.
Communicating hydrocephalus can be caused by... (3)
vit A deficiency, meningitis/meningoencephalitis (inflammatory exudate matts arachnoid villi down), neoplastic involvement of arachnoid villi
For CSF to reach the arachnoid villi from it origin in the choroid plexus of the lateral ventricles, efficient passage through __(3)__ must be unhindered; when it is hindered, it is called ___________.
Internal hydrocephalus caused by obstruction of the interventricular foramen is _________; it can be caused by... (3)
least common (b/c large size); mass involving ipsilateral choroid plexus, mass in the vicinity of the foramen.
Internal hydrocephalus caused by obstruction of the mesencephalic aqueduct is __________; it can be caused by... (3)
most common (small size, long length); hereditary stenosis, inflammatory lesions causing scarring/stricture, mass effects of inflammation/neoplasms
Hereditary stenosis causing internal hydrocephalus is the most common congenital anomaly of ________, especially those with __________.
dogs; bradycephalic skulls
Internal hydrocephalus caused by obstruction of the lateral apertures of the 4th ventricle is __________; it is caused by... (3)
second most common; congenital malformation, mass in choroid plexus/brainstem, meningitis with involvement of the choroid plexus
Hydrocephalus causes __________, which leads to... (4)
increase in intracranial pressure; expansion of fontanelles (in young), herniation of brain (mature-fontanelles ossified), ventricular expansion due to tissue atrophy, tearing of periventricular white matter/death
Transependymal edema of periventricular white matter results in ___________; there is also ________ loss of _________, resulting in __________.
demyelination; ischemia; cortical neurons; atrophy of grey and white matter (ventricular expansion)
Ventricular enlargement may decrease __________ and allow ___________.
interventricular pressure; a new equilibrium of CSF production
Causes of diminished tissue perfusion. (7)
embolism, thrombosis, trauma, external compression, vasculopathy/vasculitis, arteriospasm, interruption of systemic BP
Decreased perfusion is most important because...
lack of waste removal and nutrient supply. (to a lesser extent- hypoxia)
Hypoxia in the brain is relatively ________ and manifests as __________.