911
S-100 Protein and Neuron-Specific Enolase in
Cerebrospinal Fluid and Serum: Markers of Cell
Damage in Human Central Nervous System
Lennart Persson, MD, PhD, Hans-Goran Hardemark, MD, Jorgen Gustafsson, BSc,
Gerd Rundstrom, BSc, Ib Mendel-Hartvig, PhD, Thomas Esscher, MD, PhD,
and Sven Pahlman, PhD
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The development of a radioimmunoassay for S-100 protein is described. This method was used in
combination with a recently developed radioimmunoassay for neuron-specific enolase in cerebrospinal fluid and serum from 47 patients with cerebral infarction, transient ischemic attack, intracerebral
hemorrhage, subarachnold hemorrhage, and head injury. In cerebrospinal fluid, increased concentrations of both S-100 and neuron-specific enolase were found after large infarcts, whereas after small
infarcts and transient ischemic attacks, only neuron-specific enolase increased. The increased concentrations of S-100 and/or neuron-specific enolase were noted 18 hours to 4 days after cerebral infarction
and transient ischemic attacks. Cerebrospinal fluid concentrations of these proteins also reflected the
severity of the disease in patients with intracerebral hematoma, subarachnoid hemorrhage, or head
injury. Temporal changes in serum S-100 and neuron-specific enolase concentrations reflected the
clinical course in 4 patients. In stroke patients, the S-100 and neuron-specific enolase concentrations
may reflect the extent of brain damage and could be useful in selecting patients with major stroke for
more aggressive treatment during the acute phase. (Stroke 1987;18:911-918)
S
-100 is an acidic calcium-binding protein found
in the brain as homodimers or heterodimers of 2
isomeric subunits, a and /3, that have apparent
molecular weights of 10.4 and 10.5 kD, respectively. 12 S-lOOb 03/3-S-100) is present in high concentrations in glial cells and Schwann cells,2 S-lOOa (a/3-S100) is present in glial cells but not in Schwann cells,
and S-lOOao (aa-S-100) is found exclusively in neurons.2 There are reports of S-100 in nonnervous tissues
and cells such as adipose tissue, melanocytes, and Tlymphocytes.3"3 S-100 has been demonstrated in certain tumors such as glioma, melanoma, schwannoma,
and highly differentiated neuroblastomas (ganglioneuroblastoma and ganglioneuroma).46"9
Neuron-specific enolase (NSE, defined as y-subunit
of enolase) is predominantly present in neurons, neuroendocrine cells, and neuroendocrine tumors,10"12 although nonneuroendocrine cells, both malignant and
nonmalignant, contain the y-subunit at low concentrations.13 NSE has been demonstrated by enzymatic assay and immunoassay in tumor tissue and serum from
patients with neuroblastoma and small-cell carcinoma
of the lung and can therefore be used as a marker for
these tumors.14"18
Studies on cerebrospinal fluid (CSF) concentrations
of S-100 and NSE in patients with neurologic lesions
indicate a quantitative relation between the degree of
cell damage in the central nervous system (CNS) and
the concentration of these proteins in CSF.19"23 Thus,
S-100 and NSE could be of potential use as markers for
destructive processes in the CNS. Such markers would
be useful not only for prognostic purposes (see Sindic
et al19) but also to monitor the course of states such as
ischemic stroke, subarachnoid hemorrhage (SAH), or
severe head injury. Cell damage markers could also be
of clinical value in evaluating the effect of measures to
reduce cerebral cell damage such as vascular reconstruction, hemodilution, hyperventilation, and treatment with barbiturates, calcium blockers, or mannitol.
This study uses our radioimmunoassay (RIA) for
NSE and the newly developed RIA for S-100 and examines the concentrations of these proteins in CSF and
serum from patients with neurologic disorders involving cell damage.
From the Departments of Neurosurgery (L.P.) and Neurology
(H.-G.H.), Sodersjukhuset, Stockholm, the Department of Biochemistry and Immunology, Pharmacia AB, Uppsala (J.G., G.R.,
I.M.-H.), and the Departments of Pediatric Surgery (T.E.) and
Pathology (G.R., S.P.) Uppsala University, Uppsala, Sweden.
Supported in part by the Swedish Natural Science Research
Council, Swedish Medical Research Council, Ake Wibergs Stiftelse, Hans von Kantzows Stiftelse, HKH Kronprinsessan Lovisas
FOrening f6r BarnsjukvSrd, Ollie och Elof Ericssons Stiftelse, Karolinska Institutets Fonder, and the Swedish Society of Medicine.
Address for reprints: Dr. Lennart Persson, Department of Neurosurgery, University Hospital, Uppsala University, S-75185, Uppsala, Sweden.
Received February 21, 1986; accepted May 14, 1987.
Patients
CSF and serum were collected from patients at the
Departments of Neurosurgery and Neurology, Sodersjukhuset, Stockholm. CSF was aspirated by lumbar
puncture or via an intraventricular catheter. Serum was
obtained from venous blood. The samples were frozen
and kept at - 20° C until analyzed.
We examined CSF from 43 patients and serum from
4 patients. In some cases, CSF and serum were consecutively sampled. As controls, we used lumbar CSF
Subjects and Methods
912
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from 16 subjects investigated for symptoms such as
headache or dizziness but in whom no organic disease
could be found or who underwent myelography for
suspected lumbar disk disease.
All CSF was taken from patients or control subjects
in whom lumbar puncture or ventricular drainage were
done for other reasons. The study was approved by the
ethics committee of Karolinska Institutet, Stockholm.
Twenty-eight patients had cerebral infarction (CI) or
transient ischemic attack (TIA); 27 of these patients
were examined by computed tomography (CT, EMI
scanner CT 1010) and/or "Tc brain scintigraphy 6-25
days after the onset of symptoms. The CT scans were
classified as normal (no signs of cerebral disease),
small (hypodense area without mass effect), moderate
(hypodense area with slight mass effect), or large cerebral infarct (hypodense area with a clear mass effect).
The brain scintigraphy findings were classified as normal (no pathologic uptake), small (2-4 cm diam. uptake), moderate (5-6 cm diam. uptake), or large cerebral infarct ( > 6 cm diam. uptake). The CT scans of
patients with intracerebral hemorrhage (ICH) were divided into 3 groups: small (hyperdense area < 5 ml),
moderate (hyperdense area 5-25 ml), or large intracerebral hemorrhage (hyperdense area > 2 5 ml). The
clinical outcome of the patients was evaluated on discharge from the hospital using an outcome scale, with
minor modifications suggested by Jennett and Bond24:
0, good recovery (no residual symptoms); 1, minor
disability (resumption of normal life); 2, moderate disability (independent in daily life); 3, severe disability
(dependent for daily support); 4, vegetative state; or 5,
death. The Mann-Whitney U test was used for statistical comparison of S-100 and NSE levels in ischemic
stroke patients with lesions visible on CT and/or brain
scintigraphy (see below).
Purification of S-100 From Bovine and Human
Brain
During purification, S-100 was assayed by rocket
immunoelectrophoresis23 using antiserum prepared
against bovine a and /3 subunits of S-100 (Dakopatts
a/s, Glostrup, Denmark). S-100 from bovine brain was
prepared essentially as described by Moore26 and by
Dannie and Levine.27 All purification steps were performed at 4° C. Bovine brain was homogenized in 10
mM Tris-HCl buffer (pH 7.4) containing 5 mM
MgCl2, 0.6 mM phenylmethylsulfonylfiuoride, and
0.6 mM iodoacetic acid. After centrifugation at
100,000g for 45 minutes, the supernatant was taken for
repeated ammonium sulfate precipitations at 50, 65,
and 80% saturation, and the 80% supernatant was concentrated and dialyzed against Buffer A (10 mM TrisHCl [pH 7.5], 1 mM of ethylene diamino tetraacetic
acid [EDTA], and 1 mM 2-mercaptoethanol). This
material was adsorbed on a DEAE-Sepharose CL-6B
column (Pharmacia AB, Uppsala, Sweden), and S-100
immunoreactivity was eluted by a linear gradient of
NaCl in Buffer A running from 0 to 0.7 M NaCl.
S-100 from human brain was purified as described
by Isobe et al.28
Stroke
Vol 18, No 5, September-October 1987
Sodium Dodecyl Sulfate-Polyacrylamide Gradient
Gel Electrophoresis and Immunoblotting
The S-100 preparation was analyzed by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis
(SDS-PAGE) (gradient 12-20%) under reducing conditions as described by Laemmli.29 The proteins were
stained with 0.05% Coomassie BB G-250. The molecular weight markers used were phosphorylase b (94
kD), bovine serum albumin (BSA) (67 kD), ovalbumin (43 kD), carbonic anhydrase (30 kD), trypsin inhibitor (20.1 kD), and a-lactalbumin (14.4 kD).
Immunoblotting was performed essentially as described by Towbin et al.30 Purified S-100 protein was
run on SDS-PAGE (15-30% gradient), and the separated polypeptides were blotted onto a nitrocellulose
filter. After blocking with 5% BSA and 0.25% hemoglobin, anti-S-100 antiserum (diluted 1:100, Dakopatts) was added. After washing, 12JI-protein A (1
/ig/ral, Pharmacia) was used to visualize the S-100
subunits by autoradiography.
Radioimmunoassay for S-100
The purified S-100 was labelled with 123I, using the
chloramin T method.31 In the standard protocol for
determination of S-100 in body fluids, 0.1 ml of the
tracer (0.1 ng S-100, approximately 20,000 cpm), 0.1
ml of S-100 antiserum (1:3,600 dilution, Dakopatts),
and 0.1 ml of the sample were incubated at room
temperature overnight. Purified bovine S-100 was
used as a standard. Bound S-100 tracer was separated
from free tracer by precipitation of the immunecomplexes with sheep anti-rabbit IgG antibodies bound to
Sepharose.32 All samples were determined in duplicate, and S-100 values were expressed as ng/ml body
fluid.
Determination of Neuron-Specific Enolase
NSE was determined by a Pharmacia RIA as described by Pahlman et al,32 using human NSE as a
standard and an antiserum raised against human NSE.
Results
Purification of Bovine S-100
SDS-PAGE analysis of the purified S-100 immunoreactive material showed 1 protein band with an apparent molecular weight of approximately 10 kD (Figure
1 A). The molecular weight and the immunologic identification of the 10-kD protein during purification
strongly suggested that the purified protein was S-100.
The broad S-100 band indicated that the preparation
contained both the a and the /3 subunits. This possibility was tested by immunoblotting. Two bands corresponding to the molecular weights of the a and /3
subunits were then identified by the S-100 antiserum
(Figure 1C).
5-700 Radioimmunoassay
Autoradiographic analysis of l25I-labelled S-100
protein (Figure IB) separated by SDS-PAGE showed,
in addition to the 2 S-100 subunits, a minor impurity
not detectable by Coomassie staining (Figure 1A) or
Persson et al
S-100 Protein and Neuron-Specific Enolase in CSF
A
1
94-
B
2
9467-
67-
43-
43-
30-
30-«
2020-
—
14-
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14-
FIGURE 1. Sodium dodecylsulfate-pofyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting of purified, bovine S-100. A: Lane 1, Molecular weight markers (see "Subjects and Methods"). Lane 2, Bovine S-100 separated on
polyacrylamide gradient gel (12-20%) and stained with Coomassie BB. B: Autoradiogram ofl25l-labelled S-100 separated
by SDS-PAGE as in A. C: S-100 protein separated on 15-30%
polyacrylamide gel and immunoblotted as in "Subjects and
Methods." Arrow indicates S-100 protein.
immunoblotting (Figure 1C). Under the given conditions, RIA detected the equivalent of 1 ng S-100/ml.
Cross-reactivity of the RIA with human S-100 was
confirmed by competition experiments in which purified human S-100 protein fully competed with binding
of the bovine S-100 standard. Thus, S-100 immunoreactivity measured in this RIA, in patient CSF, and in
serum reflected the concentration of human S-100.
Cerebrospinal Fluid and Serum Concentrations of
S-100 and Neuron-Specific Enolase
Immunoreactivity in Controls
CSF S-100 values in control subjects ranged from
< 1 to 6.8 ng/ml. CSF NSE values were < 2 ng/ml in
all but 1 case (2.4 ng/ml). Mean serum concentration
of NSE in healthy controls was 7 ng/ml (SD 1.6 ng/ml,
range <2-13 ng/ml) in 152 cases,17 and the mean
serum concentration of S-100 was 5.3 ng/ml (SD 2.4
ng/ml, range 2.8-11.5 ng/ml) in 16 cases.
Cerebral Infarction and Transient Ischemic Attacks
CSF S-100 and NSE concentrations in 24 patients
with CI (12 men, 5 women; mean age 59 years) orTIA
(4 men, 3 women; mean age 58 years) are given in
Table 1. Wide variations in S-100 and NSE concentrations were noted. However, a relation emerged be-
913
tween the concentrations of S-100 and NSE in CSF and
the time between onset of stroke and lumbar puncture
(Figure 2). Normal S-100 and NSE concentrations
were noted 8 hours after the onset of stroke; CSF
aspirated between 18 hours and 4 days after the onset
of symptoms showed increased concentrations of S100 and/or NSE in 17 of 20 patients; later, lower concentrations were found. The highest concentrations of
the markers were found in patients with severe stroke,
whereas lower concentrations were obtained in patients with less severe stroke or TIA (Table 1). No CT
or brain scintigraphy changes were found in the 3 patients in whom the CSF markers were not increased
during the 18 hours-to-4 days period; these 3 patients
had minor disability. In CSF from the 7 patients with
TIA, NSE was increased in 6 and S-100 was increased
in 3; in 2, both NSE and S-100 were increased. Furthermore, the NSE concentrations were generally
higher than the S-100 concentrations in patients with
TIA, while the opposite was true for most patients with
CI (Table 1).
In Figure 3,19 patients in whom CSF was taken 18
hours to 4 days after ictus are grouped according to CT
and/or brain scintigraphy findings and divided into
groups with visible and nonvisible lesions. Compared
with controls, NSE concentration was increased in the
CSF of both the visible (p< 0.001) and nonvisible
groups (p<0.01), although higher values were obtained in patients with visible lesions (/?<0.05). Increased levels of S-100 were predominantly found in
the CSF of patients with visible lesions (p<0.01),
whereas most patients with nonvisible lesions had lower levels of S-100 (p<0.05).
In 4 patients with ischemic stroke (2 men, 2 women;
mean age 64 years), consecutive serum samples taken
at various times after ictus were analyzed. In 2 patients, 1 with a small CI and 1 with TIA, serum S-100
and NSE were within the normal range (4—8 ng/ml for
both markers). In the 2 other patients (1 moderate and
1 large CI), S-100 and NSE were increased and varied
concomitantly, and the concentrations of the markers
reflected fairly well the severity of the ischemic lesion,
as exemplified in Figure 4.
Subarachnoid Hemorrhage Resulting From
Aneurysm Rupture
CSF from 10 patients with SAH was studied. In all
but 1, CSF was obtained via an intraventricular catheter. In the 1 patient in whom CSF was sampled 8
hours after SAH, the S-100 and NSE concentrations
were normal. In CSF taken at >24 hours, the concentrations of the markers reflected the severity of the
disease (Table 1). CSF was sampled consecutively in 3
of the 10 SAH patients.
Case 1. This patient was deeply unconscious on
admission owing to rupture of an aneurysm and to a
large intracerebral hematoma. After 2 operations
(evacuation of hematoma and clipping) and a period in
barbiturate coma, he died of brain herniation. The final
deterioration was paralleled by a dramatic increase in
CSF S-100 and NSE concentrations (Figure 5 Top).
914
Stroke
Vol 18, No 5. September-October 1987
Table 1. Clinical Diagnoses, Number of Patients, and Individual S-100 and NSE Concentrations in CSF
S-100
ng/ml
Diagnosis
Cerebral infarction
NSE
ng/ml
Days from onset to
first CSF sample
CT/BS
Outcome
n=\l
8.2
<1
2.5
6
6
5
3.2
2.2
1.4
1.4
40.0
14.4
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1.6
3.2
700
3.4
7
460
Transient ischemic attack n = l
2.9
11.4
8.8
7.6
4
<1
<1
4.2
<2
<2
4.4
9
4.9
<2
<2
4.9
2
10.5
7.5
<2
5.7
25
10.5
<2
23
6.2
<2
6.6
10.5
5.2
2.9
4.1
nv/riv
1
1
1
1
1
1
1
1
0.75
0.83
1
1.17
2
3
4
6
0.75
0.33
2
nv/nv
nv/nv
nv/nv
nv/nv
nv/nv
nv/nv
nv/nv
2
nv/nv
2
small/small
1
small/ —
5*
small/small
-/-
3t
3t
small/nv
1
nv/small
1
large/small
1
4
small/nv
1
2
large/small
3
nv/nv
0
0
0
0
0
0
0
29
3
4
4
0.75
1
1.17
1.17
1.5
14
14
—/nv
-/nv/ —
—/nv
—/nv
nv/nv
NSE, neuron-specific enolase; CSF, cerebrospinal fluid; CT, computed tomography; BS, brain scintigraphy; nv, no
visible lesion; —, not performed. For definition of lesion size and outcome, see text.
*Died from lntercurrent disease 9 days after the ictus.
tSame patient.
Case 2. This patient developed angiographic vasospasm and ischemic symptoms after 2 SAHs. S-100
and especially NSE increased, and CT scan changes
compatible with infarction developed (Figure 5
Middle).
Case 3. The third patient was in good condition on
admission. Both the surgery and the postoperative period were uncomplicated, and she was discharged in an
excellent state. The levels of S-100 and NSE in CSF
were normal throughout this period (data not shown).
Other States
CSF from 5 patients with ICH was investigated (Table 1). A relation emerged between the concentrations
of the markers, especially S-100, and clinical outcome. CSF from 4 patients with head injury was also
studied (Table 1).
Case 4 had a severe head injury with acute subdural
hematoma and intracerebral contusions. The first CSF
sample was obtained about 48 hours after the trauma and
showed high concentrations of S-100 and moderately
increased NSE values, 38 and 8.6 ng/ml, respectively
(Figure 5 Bottom). After surgery, the patient was treated
with barbiturates, mannitol, and hyperventilation to control the intracranial pressure. Follow-up samples showed
falling concentrations of the markers, and the patient
recovered and was only slightly disabled after 2 months.
Two patients with prolonged coma after head injury were
investigated 6 days after trauma. Both showed normal
serial CT scans, and the diagnosis of diffuse axonal
injury was made. One showed raised concentrations of
S-100 and NSE (12 and 6.8 ng/ml); this patient died after
4.5 months. The other had normal concentrations in CSF
and was slowly recovering when discharged. The fourth
patient with head injury had a postconcussional syndrome; CSF showed normal concentrations of both
markers 30 days after trauma.
Discussion
In the present study, we used 2 newly developed
RIAs for determining S-100 and NSE. The NSE RIA
has been described previously and does not cross-react
with a and /3 subunits of enolase.32 The S-100 RIA is
based on an antiserum that recognizes both a and /3
Persson et al
S-100 Protein and Neuron-Specific Enolase in CSF
Table 1.
915
(Continued)
S-100
ng/ml
Diagnosis
Days from onset to
first CSF sample
NSE
ng/ml
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Subarachnoid hemorrhage n= 10
<1
3.8
13.8
<1
16.4
<1
>350
>350
2.2
7.4
Intracerebral hemorrhage n — 5
72.0
1.9
4.2
1.4
114
CT/BS
6
8
9
2.9
3
7
5.6
<2
<2
—
—
0-1
0-1
2
3
3
3
5
5
5
5
4
13
0.33
1
1
15.5
2.3
5
25
8.5
<2
<2
6.3
12.5
1
small/ —
1
small/ -
7
small/ —
12
4
Outcome
moderate/ —
large/ —
2
1
1
3
3
Head injury n = 4
8.6
6.8
<2
38
12
<1
2
6
6
30
<2
2.3
subunits of bovine S-100, as evidenced by the immunoblotting experiments. Furthermore, the RIA
recognizes human S-100 as shown by the competition
studies with purified human S-100 protein. CSF concentrations of NSE and S-100 in controls, determined
with these RIAs, largely agree with figures reported by
others,2123'33-33 although some authors demonstrated
higher concentrations of NSE. 3637
A conspicuous finding of the present study was that
the concentrations of S-100 and NSE in lumbar or
ventricular CSF varied according to time after the onset of symptoms. In ischemic stroke patients, concentrations of the markers were increased in CSF between
JUU
0
o
I
°
S-100
• NSE
100
o
«
LU
C/3
•
•
10
8
0
10
20
30
Days (rom onset of symptoms to CSF sampling
FIGURE 2. S-100 and neuron-specific enolase (NSE) (nglml)
in cerebrospinal fluid (CSF) ofpatients with cerebral infarction
and transient ischemic attacks in relation to time between onset
of symptoms and lumbar puncture.
1
5
1-2
1
18 hours and 4 days after the ictus. The concentrations
of the markers during this period appeared to reflect
the severity of the disease.
It should be pointed out that of the 30 patients with
CI, TIA, or ICH studied, only 1 died (of intercurrent
disease); no patient became vegetative, and only 4
became severely disabled. Thus, the resulting brain
damage in these patients was, as a whole, probably
rather restricted, yet concentrations of the markers
were increased in most cases if sampled during the 18
hours-to-4 days period. This suggests that both S-100
and NSE are sensitive markers of brain damage. A few
patients with small lesions and low concentrations of
S-100 and NSE suffered a poor outcome, probably
because the lesion was located in a vulnerable area of
the brain.
In the SAH patients, S-100 and NSE also seemed to
be sensitive markers of brain damage, and their concentrations in CSF appeared to reflect the clinical
course and severity of the disease. In some of the SAH
patients, increased concentrations were also noted later than 4 days after ictus; this may be attributed to
secondary brain damage (i.e., vasospasm). The dynamic changes in CSF concentrations of S-100 and
NSE are further illustrated by the 2 cases of SAH in
whom the markers were consecutively measured.
One rationale for analyzing both these markers is the
possibility of differentiating between gray and white
matter damage35 because S-100 is present mainly in
glial cells and NSE mainly in neurons. In most of our
916
Stroke
1000 -i ng/mL
Vol 18, No 5, September-October 1987
of recognizable cerebral ischemia, the preponderance
of NSE in the CSF of such patients may reflect a
selective vulnerability of neurons. Although TIA by
definition is a reversible state, the presence of NSE and
S-100 in CSF indicates that structural brain damage
occurs in TLA.
When the concentrations of the markers in CSF from
patients with ischemic stroke were related to CT and
100 •
10
1000 T
Visible
n-7
Non-visible
n-12
Visible
n-7
o
o
Non-visible
n-12
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NSE
S-100
FIGURE 3. 5-700 and neuron-specific enclose (NSE) (ng/ml)
in cerebrospinal fluid (CSF) sampled 18 hours to 4 days after
ictus in 19 patients with cerebral infarction and transient ischemic attack diagnosed by computed tomography andlor brain
scintigraphy. Visible lesions: S-100 mean 175.4, range 3.2700, SD 285.7; NSE mean 12, range 2-25, SD 8.7. Non-visible
lesions: S-100 mean 4.9, range < 1-11.4, SD 3.1; NSE mean
4.8, range 2-10.5, SD 2.8. Lines indicate upper limit for
controls.
0
2
10
4
12
Days after ictus
14
16
•
•
reacting pupils
operation x2
fixed pupUs
O
•
patients, both proteins were elevated in CSF if sampling was done within a certain time period. This is
probably because most of the lesions (ischemic, traumatic, or other) involved both gray and white matter.
In some cases, there was preponderance of one of the
markers. In the patients with CI, concentrations of
both S-100 and NSE as a rule increased, but in general
the increase in S-100 concentration was greater than
that of NSE. This contrasts with the findings in the TIA
patients, in whom elevation of CSF NSE concentration
dominated. The reason for the difference between CI
and TIA is unclear, but it is well established that neurons are the cells in the CNS most sensitive to ischemia.38 Assuming that TIA represents the mildest form
18
S-100
NSE
Coma-v*g«tatlv9, vasoapasm
19
21
23
27
25
29
Days after Ictus
SAH1
40
O
«
S-100
NSE
I.
30 T
UJ 20
O S-100
• NSE
8
10
8
10
12
14
16
18
20
22
Days after Injury
accident
Hours from onset of stroke to serum sampling
FIGURE 4. Serum S-100 and neuron-specific enolase (NSE)
(ng/ml) concentrations in patient with cerebral infarction.
op
op
awake, I '
obeying commands
FIGURE 5. Cerebrospinal fluid (CSF) and neuron-specific
enolase (NSE) (ng/ml) in 3 patients. Top: Case 1, subarachnoid
hemorrhage (SAH) with intracerebral hematoma; died. Middle:
Case 2, SAH with vasospasm and ischemia; severe disability.
Bottom: Case 4, severe head injury; minor disability.
Persson et al
S-100 Protein and Neuron-Specific Enolase in CSF
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brain scintigraphy findings instead of to clinical entities such as CI and TIA, a difference between S-100
and NSE emerged. In principle, NSE concentration
was increased in patients with both visible and nonvisible lesions, whereas S-100 concentration was predominantly increased in patients with visible lesions.
This suggests that the markers might distinguish between patients with larger (i.e., visible) infarcts on one
hand, and patients with smaller (i.e., nonvisible) infarcts and TIA on the other.
S-100 and NSE can also be detected in serum. In
ischemic stroke patients, the levels of the markers during the first days were related to the severity of the
lesion. It should also be pointed out that the serum
concentrations of S-100 and NSE were in the same
range as or lower than the CSF concentrations found in
patients with ischemic stroke. Thus, the increased concentrations of these markers in CSF were probably
derived from damaged cerebral tissue rather than from
serum.
In conclusion, the findings presented here indicate
that early determination of CSF and serum S-100 and
NSE concentrations in patients with cerebral lesions
mayreflectthe extent of brain damage and that repeated measurements may be useful to follow the course of
brain ischemia.
Acknowledgments
We thank Mrs. Ingegard Hjertsson and Mr. Berne
Albertsson for excellent technical assistance.
References
1. Endo E, Tanaka T, Isobe T, Kasai H, Okuyama T, Hidaka H:
Calcium dependent affinity chromatography of S-100 and calmodulin on calmodulin antagonist coupled Sepharose. / Biol
Chem 1981 ;256:12485-12489
2. Isobe T, Takahashi K, Okuyama T: S-lOOao protein is present
in neurons of central and peripheral nervous system. J Neurochem 1984;43:1494-1496
3. Hidaka H, Endo T, Kawamoto S, Yamada E, Umekawa H,
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Stroke
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KEY WORDS • S-100 protein • neuron-specific enolase •
cerebrovascular disease • cerebrospinal fluid • subarachnoid
hemorrhage
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S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell
damage in human central nervous system.
L Persson, H G Hårdemark, J Gustafsson, G Rundström, I Mendel-Hartvig, T Esscher and S
Påhlman
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Stroke. 1987;18:911-918
doi: 10.1161/01.STR.18.5.911
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