Table 3. A summary of preclinical animal literature studying the effects of surgical decompression in spinal cord injury
Reference
Brodkey et al,
1972 [6]
Species
(number)
Cats, n = 5
Injury model
Timing of decompression
Study conclusions
Weight was applied over
the dorsal surface of the
spinal cord and intact dura
Time since spinal cord
compression and/or aortic
clamping to CEP effects
Direct pressure to the spinal cord and hypotension result in additive deficits as
recorded by CEP (cortical-evoked potentials)
Croft et al,
1972 [17]
Cats, n = 15
Weight was applied over
the dorsal surface of the
spinal cord and intact dura
Graded weight (18-58 g)
and graded time (5-20
minutes)
Graded pressure (38 g for 5 to 20 minutes and 58 g for 20 minutes) on the spinal cord
produced reversible blocking of SSEP potentials
Thienprasit et
al, 1975 [61]
Cats, n = 28
A Number 3 French
Fogarty catheter was
passed through a L2laminectomy extradurally
in the cephalic direction
for 6 cm and inflated with
0.6-0.9 cc of air and
immediately deflated
No treatment versus
laminectomy at 6 hours
after SCI versus
laminectomy at 6 hours
after SCI + cooling of
spinal cord for 2 hours
In more severely injured animals (based on return of cortical evoked response),
surgical decompression and cooling offered improved outcome
Kobrine et al,
1978 [34]
Macaque
monkeys, n = 10
1 hour
Results suggested that mechanical forces of compression, rather than ischemia are
mainly responsible for the loss of neural conduction in such a model
Kobrine et al,
1979 [35]
Macaque
monkeys, n = 18
1, 3, 5, 7, or 15 minutes
These data suggest that the cause for neural dysfunction after balloon compression is
physical injury of the neural membrane, irrespective of blood flow changes; recovery
is related to length of time of compression
Bohlman et al,
1979 [4]
Dogs, n = 14
Spinal cord compression
(right, lateral) using
Fogarty catheter in the
epidural space
Spinal cord compression
(right, lateral) using
Fogarty catheter in the
epidural space
Compression model:
transducer; contusion
model: Allen weight-drop
device
4 to 8 weeks until
neurologic recovery ceased
to improve
Of the eight pressure-induced SCIs that recovered, microscopic examination was
normal in 2, central gray necrosis occurred in 2, peripheral demyelinization in 2,
and lacerations occurred in 3
Pathologic findings associated with significant paralysis: mild anterior horn gray
matter necrosis in 2, laceration of the ventral white and gray matter in 3, and no
microscopic evidence of cord damage in 1
In this study, the CEP response closely paralleled the degree of initial SCI either from
contusion or compression as well as the neurologic recovery of the animals
Dolan et al,
1980 [22]
Rats, n = 91
Spinal cord clip
compression
3 seconds, 30 seconds, 60
seconds, 300 seconds, or
900 seconds (15 minutes)
30 or 60 minutes
Aki and Toya,
1984 [1]
Dogs, n = 33
Spinal cord compression:
weight placement
Guha et al,
1987 [28]
Rats, n = 75
Spinal cord clip
compression
15 minutes, 60 minutes,
120 minutes, or 240
minutes
Nystrom and
Berglund, 1988
[47]
Delamarter et
al, 1991 [19]
Rats, n = 81
Spinal cord compression:
weight placement
1 minute, 5 minutes, and 10
minutes
Dogs, n = 30
Circumferential
constriction of the cauda
equina with a nylon
electrical cable
2-3 seconds, 1 hour, 6
hours, 24 hours, and 1
week
Zhang et al,
1993 [64]
Rats, N = not
disclosed
Spinal cord compression
(graded weight
compression)
5 minutes of compression
with varied weight: group 1
(no compression, control),
group 2 (9 g weight), group
3 (35 g weight), and group
4 (50 g weight)
Functional recovery decreased as the duration of compression increased and the force
of compression increased
With increasing compressive weights (6 g to 60 g), SEP amplitudes were
progressively more reduced and latencies more prolonged
After release of compression, amplitudes and latencies recovered at the lower
weights but were more likely to reflect greater conduction deficits with progressively
greater weights
Pathologic findings: hemorrhage and necrosis were not found in the gray and white
matter in the groups weighted with 6 and 16 g, whereas small petchial hemorrhages
and tissue necrosis were observed in the center of the gray matter in the groups
weighted with 36 and 60 g
However, there were no distinct findings in the white matter with these higher
weights
The major determinant of recovery was the intensity of compression applied to the
spinal cord; the time until decompression also affected recovery, but only for the
lighter compression forces (2.3 and 16.9 g)
Both the amount of weight and the duration of placement affect the animals’ ability
to recover, whereby a heavier weight and longer duration of placement are associated
with less recovery
All 30 dogs developed caudal equina syndrome after constriction and all dogs
recovered significant motor function 6 weeks after decompression (recovered to
walking (Tarlov Grade 5) with bladder and tail control at 6 weeks after SCI)
Immediately after compression, all 5 groups demonstrated greater than 50%
deterioration of the posterior tibial nerve SSEP amplitudes; at 6 weeks after
decompression, all 5 groups had a mean amplitude recovery of 20% to 30%; there
was no difference in recovery of SSEPs among the groups
All groups demonstrated scattered Wallerian degeneration and axonal regeneration;
there were no significant differences in the histologic findings among the 5 groups
In groups 2 and 3, lactate levels increased 6 to 7 times the basal levels in the first
fraction; group 2 levels normalized within approximately 30 minutes, whereas group
3 levels were a lot slower in recovering
Group 4 lactate levels increased 10x in the second fraction; only partial recovery was
seen in the 2-hour period
No significant change in pyruvate levels was seen in any of the groups
Inosine levels rose 0.7-0.9 uM in groups 2 and 3 and 1.4 uM in the Group 4
Delamarter et
al, 1995 [18]
Dogs, n = 30
Circumferential
constriction of the caudal
spinal cord with a nylon
electrical cable to 50% of
the diameter of the spinal
canal.
2-3 seconds, 1 hour, 6
hours, 24 hours, and 1
week
Carlson et al,
1997 [9]
Dogs, n = 12
Spinal cord compression:
hydraulic loading piston
5 minutes, 3 hours
Carlson et al,
1997 [10]
Dogs, n = 21
Cord compression
Spinal cord displacement
was maintained for 30
minutes (n = 7), 60 minutes
(n = 8), or 180 minutes (n =
6) after lower extremity
SEP amplitudes were
reduced by 50% of baseline
Dimar et al,
1999 [21]
Rats, n = 42
Contusion injury: impactor
0, 2 hours, 6 hours, 24
hours, and 72 hours
Carlson et al,
2003 [8]
Dogs, n = 16
Spinal cord compression:
hydraulic piston
Spinal cord displacement
was maintained for 30
minutes (n = 8) or 180
minutes (n = 8) after SSEP
Inosine recovery was faster than lactate with group 4 recovering completely in
approximately 40 minutes
Recovery of hypozanthine was more delayed compared with other metabolites;
complete recovery took almost 80 minutes
The dogs with immediate decompression generally recovered neurologic function
within 2 to 5 days; animals that were compressed for 6 hours or more showed no
significant motor recovery after decompression of spinal cord
Discrete areas of Wallerian degeneration and demyelination were seen in the spinal
cord of animals decompressed either immediately or at 1 hour; in contrast, there was
severe central necrosis in the spinal cord of animals that were decompressed at 6
hours or later
Regional spinal cord blood flow was reduced at the site of piston compression; in the
sustained compression group, no recovery of SSEP occurred and blood flow
remained significantly lower than baseline at 30 and 180 minutes after maximum
compression; spinal cord decompression was associated with an early recovery of
blood flow and SSEP recovery; by 3 hours, blood flow was similar in both the
compressed and decompressed groups, although SSEP recovery occurred only in the
decompressed group
SEP recovery was seen in 6 of 7 dogs in 30-minute, 5 of 8 dogs in 60-minute, and 0
of 6 of the dogs in 180-minute compression group
Regional spinal cord blood flow at baseline decreased after stopping dynamic
compression; reperfusion flows after decompression was inversely related to duration
of compression
Reperfusion flows measured as the interval change in blood flow between the time
dynamic compression was stopped to 5, 15, or 180 minutes after decompression were
significantly greater in those dogs that recovered SEP (p < 0.05)
Spinal cord decompression within 1 hour of SEP loss resulted in significant
electrophysiological recovery after 3 hours of monitoring
There was a progressively more severe central and dorsal cavitation as the time of
spinal cord compression increased
Midsagittal sections demonstrated progressive cephalad and caudal cord necrosis and
cavitation, which worsened the longer the duration of compression; these changes
were most severe in the 24- and 72-hour specimens
A shorter time of compression was associated with better neurologic function at both
early and late time points
Lesion volumes as assessed with MRI were smaller in the 30-minute compression
group than the 180-minute compression group (p = 0.04)
Hejcl et al,
2008 [30]
Rats, n = 23
Spinal cord transection
Rabinowitz et
al, 2008 [50]
Dogs, n = 18
Circumferential
constriction of the
thoracolumbar junction
with a nylon electrical
cable
amplitudes were reduced
by 50% of baseline
The 30-minute compression group showed smaller lesion volume (p < 0.001) and
greater percentage of residual white matter (p = 0.005) than the 180-minute
compression group
HEMA-MOETACl
hydrogel was inserted right
away after SCI (acute
group) or 1 week after SCI
(delayed group)
Group 1: decompression at
6 hours +
methylprednisolone
Group 2: decompression at
6 hours + sham
Group 3:
methylprednisolone only
There was no significant difference in histopathologic examination of spinal cord
between the acute and delayed implantation groups; there were no significant
differences between the two treatment groups with regard to the BBB scores
Decompression within 6 hours (groups 1 and 2) showed significant neurologic
improvement when compared with the no decompression (group 3);
methylprednisolone did not significantly affect outcome; there was no statistical
difference in the percentage of cord involvement histologically among the 3 groups;
group 3 did show greater involvement below the level of the lesion
SCI = spinal cord injury; SEP = sensory-evoked potential; SSEP = somatosensory-evoked potential