Glial cells (stromal cells) Oligodendrocytes ... - CSU PVM 2014

Glial cells (stromal cells)
Oligodendrocytes…gliosis/satellitosis
Oligodendrocytes are present in subcortical white matter--responsible
for production and maintenance of the myelin sheath
If an agent damages or kills these in utero==>hypomyelogenesis (can
be caused by distemper)
If happens after birth (body fails to upkeep or maintain myelin):
dysmyelogenesis
Satellitosis = proliferation of oligodendrocytes around injured neurons
Neurons cannot proliferate
Oligodendrocytes produce myelin
1

Astrocytes…gemistocytic/astrocytosis /Alzheimer type 2 cells
Astrocytic reaction is typically viewed as a reparative response in the CNS, akin to
scarring in nonneural tissues.
Astrocytes respond to injury by hypertrophy and limited proliferation.
The section to the left is from a dog with a focally extensive area of infarction. The
section is stained by GFAP (immunohistochemistry). With this particular stain you can
visualize the processes (normally inconspicuous in H and E stain).
Note the large number of astrocytes (hyperplasia or astrocytosis) with lot of
processes (hypertrophy or astrogliosis).
Fibrous have more dendrites
Protoplasmic have more cytoplasm
Fibrous forms glial limiting membrane
Astrocytes will proliferate (astrocytosis ) and hypertrophy (astroglyosis) in
response to injury to nervous tissue
Protect neurons from too much electrolytes or fluid (will sacrifice self because
they are replaceable and neurons are not)
2

Another astrocytic response is development of visible cytoplasm. These plump active
astrocytes are termed gemistocytic astrocytes.
The photograph to the left is from a dog infected with CD virus
Alzheimer type II cells
They appear as paired swollen clear astrocytic nuclei. They manifest in metabolic
disturbances when the liver or kidney is damaged (hepatoencephalopathy or uremic
encephlaopathy).
Alzheimer II cells have no relation to the disease
When astrocytes react, they hypertrophy and become more visible: look like plump
cells with abundant eosinophilic cytoplasm and eccentric nuclei
Called gemistocytic astrocytes
Will see these in canine distemper
In uremia or liver damage, see Alzheimer II cells
4

Brain macrophages/microglial cells…glial nodules/neuronphagia/gitter cells
Microgliosis refers to the proliferation of resident macrophages of the CNS
(microglia).
The proliferation may be diffuse or focal.
Glial nodules – are hall mark of viral encephalitis
Neurons are degenerating and surrounded by a proliferation of oligodendrocytes
(satellitosis) and macrophages (are eating dead neurons, neuronphagia).
Microglia are normally present in a resting stage until something invades the brain
and activates them
When activated, they proliferate and form glial nodules
Surround affected neuron and eat it: neuronophagia
If there is lipid turnover, glial cells will transform into Gitter cells
Will remove debris
Now we have three types of reaction to insult: satellitosis, astrocytosis, glial nodules
5

Macrophages in the CNS are either activated microglia or monocytes recruited from
circulation
Remember monocytes in circulation macrophages in tissues
6

Inflammatory cells surround CNS vessels in the “Virchow-Robin” space giving the
characteristic appearance of perivascular cuffing.
Remember that there are no lymphatics in the brain.
If pigs are not watered regularly especially in winter, the high salt diet with no water
makes blood hypernatremic, The fluid will leave the brain to more hypertonic blood
resulting in brain dehydration. When the pig subsequently drank excessive water the
blood turns into hypotonic. This will result in massive flow of water back to the brain.
The reason for accumulation of Eosinophils in the brain is unknown.
No lymphatics in the brain
Have to keep circulation in the brain unidirectional--lymphatics can't always do
that
Space around vessel = Virchow Robin space
Inflammatory cells exit blood vessel and surround vessel in multiple rows
(perivascular cuffing)
Eosinophils accumulate in Virchow Robin space in salt poisoning (not known
why)
CHF: accumulating water around vessels which appear as clear spaces
7

Status spongiosis
Is a nonspecific term that describes rarefied brain parenchyma (full of holes).
It can occur as a result of demyelination due to swelling of the neuropil (astrocyte
and oligodendrocytes).
Malacia
Malacia literally means softening
9

=softening of the spinal cord
poliomyelomalacia would be in gray matter,
leukomyelomalacia whould be in white
10

Astrocytes come to fill this space = astrocytic scars
Areas of liquefaction in the brain do not generally heal by fibrosis (we do not have
proper C.T. in the brain except near the meninges). Typically macrophages, gitter cells)
enter the area to remove the debris, leaving a cyst or cavity e.g. digestion chambers.
11

The arrow are pointing to the single layer of ependymal cells that lines the brain
ventricles and spinal cord central canal. VL= ventricular lumen
These cells are cuboidal to columnar and are joined by tight junctions.
Neoplasia can occur in the ependyma, ependymoma, which can obstruct the outflow
of CSF resulting in obstructive hydrocephalus.
Ependymitis may be seen with viral infections e.g. FIP in cats
The lateral ventricles of the brain to the lower right are mildly dilated. FIP and
resultant ependymitis along with accumulated exudate resulting in obstruction to the
outflow of CSF hydrocephalus (obstructive again).
One layer of tightly adhered cuboidal cells
Tumor of these cells might obstruct CSF flow
With no room to expand, get dilation and pressure atrophy
Animal will head press
12

Choroid plexus forms CSF
They project into lateral, third and fourth ventricles.
Ependymitis? Think FIP
Choroid plexitis? Think CDV
Canine distemper can infect choroid plexus cells virus is shed into the ventricular
system. This would spread the virus via the CSF.
13

Four types of cerebral edema--know why each occurs
Mostly associated with swelling and trauma
First 48 hours most critical
Midline shifted to right = swelling coming from left
Asymmetry, left is larger
15

Vasogenic: integrity of vessel is affected. No change in the forces that control
blood flow
Cytotoxic: astrocytes most affected. If they fail, fluid will next affect neurons.
Usually occurs due to ischemia
Interstitial: forces of blood are altered
Osmotic: one of three organs will usually be affected--liver (no albumin), kidney
(protein losing enteropathy), GI (protein losing enteropathy)
Heart also can be (CHF - fluid going to third space)
16

2-23-2012
17

How to differentiate between edema and artifact?
With edema, there will be a glial response: Alzheimer type II cells,
astrocytes, etc.
18

Vasogenic edema is a common complication of :
- Traumatic
- Inflammatory
- Hemorrhagic
Lesions in the CNS.
So it can be seen in a variety of situations such as contusions, space occupying
masses (neoplasia, abscess, hematoma and parasitic cysts). Also endotoxemia and
sepsis can render CNS vessels leaky.
Note the swelling and enlargement of left side this dog brain (Neoplasia).
In the photograph to the right, note the reddened area of contusion on the left
hemisphere. You can call this leptomeningeal hemorrhage.
Affected side is swollen and gyri are flat
Both trauma and edema in brain lead to energy failure and death of
neurons... and you can't fix 'em
19

1. e.g. space occupying lesion
aa occluded by pressure = ischemia
stoppage of drainage = venous obstruction
2. Vitamin B1, thiamine, is
important for brain function
3. e.g alcohol (ethylene glycol)
4. e.g. mannosidase deficiency
20

The schematic depicts normal cell hydrodynamics.
What happens if there is failure of the Na-K pump in the brain?
More sodium accumulates inside the cells this would be followed by influx of
water resulting in swelling of cells.
Causes:
Hypoxia-ischemia.
21

An unfortunate series of events:
Softened area has to be removed
with Gitter cells
At this point, it is irreversible
Replace dead neurons with
asctoryces ==> astrocytic
scar
If, after injury, reperfuse too quickly, can have reperfusion injury
22

Neurons release glutamate into synaptic cleft
Astrocytes reduce glutamate to glutamine and release back into synaptic
cleft
Taken back up by neuron and reused
NADH is important in the conversion of glutamate to glutamine
With disruption to the Na/K pump, enzyme activity reduced and ammonium
accumulates in the astrocyte
Glutamate accumulates, exerts its excitatory effect, cells run out of energy
23

eversible irreversible
26

= most dangerous
Take home msg:
Reperfusion injury: free radicals
Increased ammonium ==> decreased energy
Point of free radical formation =
irreversible
28

Hypoxia-ischemia is one of the most common causes of cytotoxic edema.
Anoxia associated with seizure activity of cardiopulmonary arrest during anesthesia.
This dog suffered from cardiac arrest.
29

In nonspecific cytotoxic edema, astrocytic swelling, characterized by nuclear swelling,
chromatin dispersion and watery cytoplasm. Oligodendrocytes, neurons, and
endothelium may also well.
30

This cat has been poisoned with the rodenticide brometahlin, resulting in cytotoxic
edema, particularly severe in oligodendrocytes resulting in intramyelinic edema and
thus splitting of myelin sheaths. Also hexachlorophene.
In the upper left, note the compact nature of normal myelin sheath in electron
micrograph.
In the lower photograph, the cat poisoned with bromethalin, intramyelinic edema led
to splitting of the myelin.
31

Water intoxication/Salt poisoning
Increased body hydration caused by excessive intravenous infusions, compulsive
drinking, or altered antidiuretic hormone.
Increased body hydration produces hypotonic plasma and fluid moves from the
plasma into the normally hypertonic brain tissue. Fluid accumulation is generally
intracellular.
32

gyri flattened due to
increased pressure
Edema may cause herniation especially in Vasogenic edema.
Shaken baby
As the brain enlarges, it can herniate in several places. Herniation can occur into
three places.
1- Cerebellar vermis herniates through the foramen magnum (also called coning or
lipping of the cerebellum).
2- Para hippocampal gyri beneath the tentorium cerebelli (transtentorial herniation).
3- Cingulate gyrus herniation under the falx cerebri (falcine herniation).
33

Hypothyroidism is most common cause of
atherosclerosis in dogs
possibly a parasite responsible
for occlusion of brain vessels
34

potential
for
emboli =
more
deleterious
than stable
plaque
36

Dog in backyard running suddenly sits down and yelps, can't walk.
Nucleus pulposis protrudes and occludes venous flow--no drainage from
the corresponding part of spinal cord--venous infarct and liquefactive
necrosis, malacia
Usually in lumbosacral area, so hindlimbs more affected
37

Vasogenic edema and dead neurons
Possibly cuterebra obstructed the veins
38

Right side obliterated, will have left-sided defects
39

The right cerebral hemisphere is atrophied due to massive necrosis and finally
collapsed.
40

Not as much as a problem for monogastrics
Ruminants have a & b sulfate reducing bacteria
Balance between the two is important
They produce two things:
Hydrogen sulfide (mostly removed by eructation)
Reduced sulfite
Amount of Cu, Fe, Zn, CHO, fiber is important for maintaining
appropriate balance between the two types of bac-t
When excess sulfur ingested, favors production of the hydrogen
sulfide, which is toxic (paralyzes oxidative enzymes) ==> kills neurons
Also need to be careful with manure--can contain hydrogen sulfide and
disturbing it leads to gas release ==> cows drop dead!
42

Grey matter
44

Cortex damage, white matter OK
Weakness, blindness, lateral recumbency, paddling with feet
Either thiamine deficiency or sulfate excess can cause this
Dx: between the two--thiamine deficiency fluoresces under wood's lamp
45

= thiamine deficiency
47

left
subdural hemorrhage
48

hematoma = circumscribed
collection of blood
most dangerous
50

often not too
horrible
can't do much
surgery here
worst type - near vital structures,
e.g hypothalamus
51

Repeated trauma results in brain swelling
associated with apoptosis!
52

Instantaneous death in horses caused by rearing -- basisphenoid bone
lacerates vessels to brain -- huge hemorrhage smooshes all that
important stuff in the brain stem
53

will see large hemorrhage
55

espiratory center, etc affected
56

Brain ricochets off opposite side of skull
58

2-27-2012
Hansen Type I
Hansen Type II
59

spinal segments subjected to sudden trauma--adjacent structures
overlay each other--massive necrosis of neurons
or
e.g. car accident
60

HBC, lots of hemorrhage
61

Common in older animals
Health of IVD can't be maintained, so it protrudes and starts impinging on
spinal cord with increasing severity
Instead of vasogenic edema, hemorrhage, necrosis in both grey and white
matter (like you would see with fast spinal cord damage), have Wallerian
degeneration in white matter only. Will see digestion chambers on histo.
63