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Alzheimer’s Disease Review 4, 19-22, 1999
19
Degenerative Changes in the Cerebral Cortex in
Swayback Disease Lambs
A.O. Adogwa, T. Alleyne and A.Mohammed
Faculty of Medical Sciences, University of the West Indies, St. Augustine, Trinidad
Summary
The study was undertaken to determine if there were differences in the degree of degenration in different parts
of the cerebral cortex in swayback disease in lambs. Histopathologic sections from the frontal, occipital,
pyriform parietal lobes, the hippocampus, caudate nucleus showed that the hippocampus was the least affected.
Key words: neuropathology, hippocampus, caudate neucleus, necrosis, cavitation, vacuolation
Swayback is a disease of lambs and kids of world wide
distribution characterised by hindlimb incoordiantion. Severely affected lambs may be paraplegic at birth. Affected
lambs may be paraplegic at birth. Affected lambs may be
blind. Slightly affected lambs may have weakened
hindlimbs and may be unable to stand but those that are
able to move do so with an unsteady gait and swaying motion.
The associationof copper deficinecy with the pathologic
changes in swayback disease has been established by several people. The low copper levels in the blood is either as
a result of low copper content in pastures which the animals
graze or due to interference with copper metabolism by some
elements (molybdenum, sulphur and iron) [Mc Dowell et
al., 1993]. In Trinidad swayback is a fairly common disease. Swayback disease in Trinidad is most likely as a result
of low levels of copper in the pastures since copper levels
of grasses in Trinidad have been found to be extremely low
[Youssef and Brathwaite, 1987]. Some swayback cases
develop in utero so that the animals die soon after birth. In
other cases, the disease develops within the first six months
of life. In Trinidad both types of swayback disease occurs.
Histopathologic diagnosis of swayback is usually based on
lesions in the brainstem, the spinal cord and the cerebellum
[Fell, 1987]. The lesions of this disease are found in the
entire brain and spinal cord but the most remarkable lesions are found in the motor neurons of the brainstem, spinal cord and the cerebellum, [Roberts, et al. 1966, Seaman
and Heartley 1981]. Even though lesions in the cerebral
cortex have been well documented, it is not yet known if
Address correspondence to: Dr. A.O. Adogwa, Faculty of Medical
Sciences, University of the West Indies, St. Augustine, Trinidad
Alzheimer’s Disease Review (ISSN 1093-5355) is published by
the Sanders-Brown Center on Aging, University of Kentucky.
It is available online at: http://www.coa.uky.edu/ADReview/.
©1999, University of Kentucky. All rights reserved.
different parts of the cerebral cortex are equally affected.
The objective of this study is to compare the histopathological lesions of this disease in different parts of the cerebral cortex.
Materials and Methods
Brains from four lambs affected by swayback were used
for the study. The brains were fixed in 10% neutral buffered formalin for two weeks. Specimens were taken from
the occipital, parietal, frontal, lobes, the hippocampus and
pyriform lobes. The specimens were further fixed in 10%
buffered neutral formalin for another two weeks before processing. The tissues were processed for normal histology
and stained with hematoxylin and eosin. The main pathologic lesions which have been reported and which were
found in swayback disease in this study are: (1) Vacuolation and cavitation; (2) Neuronal necrosis; (3) Glia infiltration; (4) Vascularisation; (5) Perineursonal vacuolation;
(6) Perivascualr vaculation. Of these the most common lesions are 1,2,3,5. These were the ones used for the evaluation. For each slide, five readings were taken from five parts
of the slide. Each pathologic lesson is graded as: + (mild),
++ (moderate), +++ (severe), ++++ (very severe). The mean
of the five readings for each lesion per slide was recorded
as the score for that slide. The total of all the mean scores is
recorded as the final score for the part of the brain. The
score from different parts of the brain were then compared
to determine the relative severity of the lesions.
Results
Neurodegenration of the brain is manifested in several ways.
The most common features of which are: cavitation and
vacuolation. Others include, Neuronal necrosis; Glia infiltration; Vascularisation; Perivascular necrosis; and
Perineuronal necrosis.
Adogwa et al.
Swayback Disease 20
Fig I. shows vacuolation and cavitation of varying sizes in
the neuropil. Cavitation is evidenced by slit-like areas of
necrosis. In some cases this shows as cracks in the white
matter. The molecular layer is usually less affected. The
lesions are not confined to any particular layer or layers but
the deeper areas of the cortex are usually more badly affected. These become more numerous and larger in the
deeper parts of the gray matter bordering the white matter.
In some cases there is radial necrosis. In severely affected
cases, large cavities occur in the neuropil.
Fig. I. A section of the cerebral cortex showing cavitation. Arrow
shows remnant of a necrotic cell body in a large space.
Necrosis of neurons occur in different forms. The pyramidal cells are usually more severely affected (fig. 2). These
cells undergo coagulative necrosis in which the soma are
homogeneously dark red. In some cases they lose their
outline and disintegrate or lose their staining. Usually no
nucleus or nucleoli can be differentiated. The granule cells
lose clear nuclear boundaries. In some cases the cytoplasm
loses its characteristic nissl stain. In severe cases the soma
undergo liquefactive necrosis, is rebsorbed leaving empty
cavities. The layers of the cortex containing pyramidal cells,
i.e., the outer pyramidal layer and inner pyramidal layer are
severely affected.
Fig 2. A section showing dead pyramidal cells
Glia infiltration is a very common feature of
neurdegeneration in swayback. In mild cases, there is an
increase in the number of glia cells in the area of degeneration. In most cases with severity of the condition gliosis
become marked (fig. 3). Satellitosis is a common feature in
which dead cells are surrounded by glia cells. In some cases
the glia cells are plump an rounded and in other cases they
Table I: Mean scores for each of the lesions and the total
scores of the lesions
Brain I
H
i
p
p
o
c
a
m
p
u
s
P
y
r
i
f
o
r
m
l
o
b
e
C
a
u
d
a
t
e
n
u
c
l
e
u
s
O
c
c
i
p
i
t
a
l
l
o
b
e
F
r
o
n
t
a
l
l
o
b
e
P
a
r
i
e
t
a
l
Brain II
l
o
b
e
H
i
p
p
o
c
a
m
p
u
s
P
y
r
i
f
o
r
m
l
o
b
e
C
a
u
d
a
t
e
n
u
c
l
e
u
s
O
c
c
i
p
i
t
a
l
l
o
b
e
F
r
o
n
t
a
l
l
o
b
e
P
a
r
i
e
t
a
l
Brain III
l
o
b
e
H
i
p
p
o
c
a
m
p
u
s
P
y
r
i
f
o
r
m
l
o
b
e
C
a
u
d
a
t
e
n
u
c
l
e
u
s
O
c
c
i
p
i
t
a
l
l
o
b
e
F
r
o
n
t
a
l
l
o
b
e
P
a
r
i
e
t
a
l
Brain IV
l
o
b
e
H
i
p
p
o
c
a
m
p
u
s
P
y
r
i
f
o
r
m
l
o
b
e
C
a
u
d
a
t
e
n
u
c
l
e
u
s
O
c
c
i
p
i
t
a
l
l
o
b
e
F
r
o
n
t
a
l
l
o
b
e
P
a
r
i
e
t
a
l
l
o
b
e
Vacuolation and Cavitation
3
1.5
1
1
2
2.5
Vacuolation and Cavitation
1
2.5
3
3
2
3
Vacuolation and Cavitation
1
1
1
2
1.5
2
Vacuolation and Cavitation
1
1
2.5
3
1
2.5
Neuronal necrosis
3
2.5
3
3
3
1.5
Neuronal necrosis
2
3
3
3
1.5
2
Neuronal necrosis
1
2
3
1.5
2
2
Neuronal necrosis
2
3
2.5
1
3
2
Glia infiltration
2
2.5
3
2
2
2.5
Glia infiltration
1
3
3
1
2
2
Glia infiltration
3
3
3
1.5
1.5
2
Glia infiltration
2
3
3
2
2
3
Perineuronal vacuolation
1
1
2
2
1
1
Perineuronal vacuolation
1
1.5
1
1
1
1.5
Perineuronal vacuolation
1
1
2
1
2
1.5
Perineuronal vacuolation
1
2
1
2
2
1.5
Total
9
7.5
9
8
8
7.5
Total
5
10
10
8
6.5
8.5
Total
6
7
9
6
7
7.5
Total
6
9
9
8
8
9
Alzheimer’s Disease Review 4, 19-22, 1999
Adogwa et al.
Swayback Disease 21
Vascularisation occurs but only in some cases. Where it
occurs, there is a gradation. In several cases there are numerous capillaries in the gray matter. These do not seem to
be confined to any layer or layers.
Perineuronal vacuolation ranges from a small space surrounding each neuron to marked spaces surrounding the
cell bodies (fig. 4). In some cases the cell bodies are
shrunken leaving large spaces.
Fig 3. A section of the cerebral cortex showing cavitation and
marked gliosis. Numerous dark dot-like structures are glia
cells.
are dark and rod like. Satellite cells are usually plump and
rounded. The satellite cells in some cases are surrounded
by clear zones of necrosis indicating that they are elaborating substances that dissolve the tissue around them. In some
severe cases the entire field is filled completely with glia
cells masking the neurons in the field.
Fig. 4. A section of the cerebral cortex showing dead neuron and
perineuronal vacuolation. Arrows show dead cells undergoing
resorption and leaving large spaces.
Table 2:Total scores from each of the brains and regions.
H
i
p
p
o
c
a
m
p
u
s
P
y
r
i
f
o
r
m
l
o
b
e
C
a
u
d
a
t
e
n
u
c
l
e
u
s
O
c
c
i
p
i
t
a
l
l
o
b
e
F
r
o
n
t
a
l
l
o
b
e
P
a
r
i
e
t
a
l
l
o
b
e
Brain I
9
7.5
9
8
8
7.5
Fig. 5. Marked gliosis (dark spots). Arrows indicate perivenous
cavitation.
Brain II
5
10
10
8
6.5
8.5
Discussion
Brain III
6
7
9
6
7
7.5
Brain IV
6
9
9
8
8
9
Total
26
33.5
37
30
29.5
32.5
The association of degenerative changes in the central nervon
system of swayback lambs and low levels of copper in the
blood and liver has been established by many workers.
Cavitation and vacuolation, extensive damage to cortical
neurons, gliosis and perivenous and perineuronal vacuolation have been reported by several researchers [Roberts et
al., 1966; Howell, 1968; Heartly, 1981; Inglis et al., 1986;
Fell, 1987]. The vacuolation and cavitation give severely
affected brains a spongy appearance. The vacuolation and
cavitation are sometimes due to empty spaces left after
From table 2 above the total score for the hippocampus is
the least and that of the caudate nucleus is the highest. The
pyramidal, the occipital, the parietal and the frontal lobes
seem to be fairly equally affected.
Alzheimer’s Disease Review 4, 19-22, 1999
Adogwa et al.
cell death and resorption; perivenous vacuolation and degeneration of the neuropil. Extensive damage to cortical
neurons is a common feature of this disease (Seaman and
Heartly, 1981). The pyramidal cells are more severely affected than the granule cells. The pyramidal cells are large
cells which send their axons into the white matter and are
responsible for the output from the cerebral cortex. The
purkinje cells of the cerebellum, motor nuclei of the
brainstem and the neurons of the ventral gray of the spinal
cord are all efferent neurons and are all badly affected.
Necrosis of neurons is accompanied by gliosis which is one
of the most characteristic features of this disease.
Astrogliosis has been frequently found in connection with
swayback [Fell, 1987; Howell, 1968]. The role of glia cells
has not been adequately investigated in swayback disease.
Defective oligodendroglia as a result of the decrease in cytochrome oxydase has been proposed as the cause of myelin aphasia and demyelination that is seen in this disease
but the role of microglia and astroglia in the disease has not
been properly investigated. Microglia have been implicated
in several central nervous system disorders such as stroke,
multiple sclerosis and Alzheimer’s disease in man and may
be involved in swayback as well.
Activation of microglial cells followed by reactive astrocyte changes has been known to contribute to brain inflammation and neuronal damage in neurodegenerative diseases
by the release of reactive oxygen free radicals. The extensive damage to cortical neurons in swayback disease may
be caused by the neurotoxic substances released by these
glia as in Alzheimer disease.
Several hypothesis have been advanced to explain the pathophysiology of swayback disease. Impairment of oxygen
diffusion due to cerebral edema combined with occlusive
pressure on cerebral blood vessels has been proposed to
account for some of the degenerative changes [Fell, 1987].
It has also been suggested that decreased activity of copper
containing enzymes contribute largely to the pathophysiology of the disease. Cytochrome c - oxidase activity has
been shown to be significantly lower in the brain tissue of
swayback lambs than the brain from clinically normal lambs
[Mills and Williams, 1962]. Copper is an essential component of several enzymes such as caeruloplasmin, dopamine, superoxide dismutase, lysl oxidase, cytochrome c oxidase and tyrosinase. Superoxide dismutase is necessary to
remove free radicals which can cause peroxidation in brain
tissues a decrease of which can contribute to demyelination since dangerous free radicals can not be removed ef-
Alzheimer’s Disease Review 4, 19-22, 1999
Swayback Disease 22
fectively from the brain tissue (Prohaska, 1987). Decreased
cytochrome oxidase may result in reduced phospholipid
synthesis which affects the integrity of cell and organelle
membranes and also myelination (Mills and Williams,
1962).
The results of this study show that the hippocampus is the
least affected and the caudate nucleus is most highly affected. The caudate nucleus is part of the extrapyramidal
pathway which is severely affected in swayback. The
pathognomonic lesions of this disease are vacuolation, chromatolysis and necrosis of these large motor neurons in the
brainstem nuclei and ventral horn of the spinal cord (Barlow,
1991). The hipocampus is not a motor centre which may
explain why it is not so badly affected. It can not be determined from this study whether the differences that exist
between the cortical areas is significant or not. A more comprehensive study involving a larger number of brains and
more areas of the cerebrum is currently being undertaken
in order to determine the significance of the differences.
References
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Copper in Animals and Man. (J. Howell and J. Gawthorne,
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Howell, J. (1968). Observations on the histology and possible
pathogenesis of lesions in the central nervous system of sheep
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Inglis, D.M., Gilman, J.S., and Murray, I.S. (1986). A farm
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