This is a journal critical appraisal taken from Gautier et al. Journal of Neuroinflammation 2014, 11:96 http://www.jneuroinflammation.com/content/11/1/96

1. Impact of the Neutrophil Response
to Granulocyte Colony-Stimulating
Factor on the Risk of Hemorrhage when
Used in Combination with Tissue
Plasminogen Activator during the Acute
Phase of Experimental Stroke
Vita Kusuma Rahmawati
Gautier et al, Journal of Neuroinflammation 2014, 11: 96
Journal Reading
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2. 2VIT

3. Introduction
• Granulocyte colony stimulating factor (G-
CSF) is a hematopoietic cytokine initially
used in the treatment of neutropenia for its
effects on proliferation and maturation of
the granulocyte cell line.
• G-CSF displayed a neuroprotective effect
when used during experimental stroke by
both decreasing the infarct size and
improving motor function recovery.
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4. Introduction
• However, the tPA-therapeutic window is
limited due to induced-hemorrhages.
• The objective of this work was to analyze
the impact of G-CSF on the risk of
hemorrhage when used in combination
with tPA during the acute phase of an
experimental ischemic stroke.
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5. Method
• Blood samples were collected before
surgery (MCA occlusion).
• Samples received G-CSF or 0.9% saline
subcutaneously just before tPA.
tPA (+)
20
tPA (-)
20
13  evaluation of infarct,
hemorrhage, and neutrophil infiltration
7  vasoreactivity analysis
Non MCA-occlusion:
4 receiving G-CSF treatment
4 receiving 0.9% saline treatment
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6. Method
Neutrophil count on peripheral blood before surgery, 24 h, and 72 h of
reperfusion
Evaluation of infarct and hemorrhage (quantifying infarct volume)
Myeloperoxidase immunohistochemistry analysis (assaying MPO
which expressed by neutrophil cells)
Vasoreactivity analysis (measuring lumen diameter)
MMP-9 analyzed on gelatin zymography
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7. Statistycal Analysis
SAS software
version 9.3
P<0.05
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8. Results
• Physiological Parameters
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9. Results
• Neutrophil response to G-CSF treatment
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10. Results
• Effect of G-CSF treatment on the risk of hemorrhage
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11. Results
• Effect of G-CSF treatment on the risk of hemorrhage
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12. Results
• Effect of G-CSF treatment on the risk of hemorrhage
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13. Results
• Effect of G-CSF treatment on endothelial
function of cerebral vessel
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14. Results
• Effect of G-CSF treatment on endothelial
function of cerebral vessel
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15. Results
• Effect of G-CSF treatment on neutrophil infiltration and
cerebral infarction size
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16. Results
• Effect of G-CSF treatment on neutrophil infiltration and
cerebral infarction size
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17. Results
• Effect of G-CSF treatment on MMP-9
release from neutrophil degranulation
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18. Discussion
• G-CSF administered in combination with
tPA during the acute phase of cerebral
ischemia worsened the risk of
hemorrhage.
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19. Discussion
In Infarct Region
• The neuroprotective effect is probably
independent from G-CSF’s action on
neutrophils; directly related to G-CSF’s
effect on neurons: inducing neurogenesis,
anti-inflammatory, and anti-apoptotic
mechanisms.
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20. Discussion
• In the Circulation
ischemia tPA treatment + G-CSF
Increase of peripheral neutrophilLeucocytosisMMP-9
Changes in arterial endothelial cells
Extravasation of RBC
Hemorrhage
BBB damage
Tissue injury
Edema formation
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21. Conclusion
The potential hemorrhagic risk in
administering G-CSF in combination with
tPA during the acute phase of cerebral
ischemia, probably though vascular
alterations mediated by the MMP-9 release
from peripheral neutrophils.
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22. 22VIT

23. Journal Search
Problem Intervention Comparison Outcome
Male
spontaneously
hypertensive rats
with middle
cerebral artery
occlusion
(MCAO) of
cerebral
ischemia
Tissue
Plasminogen
Activator (tPA) in
combination with
Granulocyte
Colony-
Stimulating
Factor (G-CSF)
Tissue
Plasminogen
Activator
Risk of
hemorrhage
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24. Design, Focus, and Worksheet
Design True experimental
Journal focus Prognosis
Worksheet
Prognosis
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25. Journal Critical Appraisal
RAMMBO Validity
Worksheet
Prognosis
Answer
Recruitment Was a defined
representative sample
of patients assembled
at a common (usually
early) point in the
course of their
disease?
Yes
Allocation How were patients
treated?
Yes
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28. Journal Critical Appraisal
RAMMBO Validity
Worksheet
Prognosis
Answer
Maintenance Was the comparable
status of the study
groups maintained
through equal
management?
Yes
28
p.3
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29. Journal Critical Appraisal
RAMMBO Validity
Worksheet
Prognosis
Answer
Maintenance Was the follow up has
been done in enough
and adequate time?
Yes
29
p.2
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30. Journal Critical Appraisal
RAMMBO Validity
Worksheet
Prognosis
Answer
Maintenance Was 80% minimally of
the subject could
follow the follow up
until the end of the
research?
Yes
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31. Journal Critical Appraisal
RAMMBO Validity
Worksheet
Prognosis
Answer
Measurement
Blinding
Outcome
Were the subjects and
assessors kept ‘blind’
to which treatment was
being received
and/or were the
measures objective?
Yes
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34. Journal Critical Appraisal
Importancy
Worksheet
Prognosis
Answer
Were the statistical and
clinical meaning from this
research can be known
well?
Yes
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35. Journal Critical Appraisal
Importancy
Worksheet
Prognosis
Answer
What kind of measurement that
was used and how much the effect
of the intervention can related to
the outcome of the subject?
OR measurement, but not
described well in statistical
analysis.
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36. Journal Critical Appraisal
Importancy
Worksheet
Prognosis
Answer
Could the outcome of this
research were merely
accident?
p-value?
Confidence interval (CI)?
p-value: <0.05 and OR 1.4
with 95% CI, so the
outcome were not happen
accidentally.
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37. Journal Critical Appraisal
No Applicability Answer
1 Were the patient quite similar to the patients in the
study?
YES
2 Were the indicator in this study can be applied to the
management of patients in your neighborhood?
YES
3 Were the outcomes of this research important for your
patient?
YES
4 Will the potential benefit is greater than the potential
harm when this indicator is applied to your patients ?
YES
5 Will the results of this research can be integrated with
the values ​​and expectations of your patients ?
YES
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38. Journal Critical Appraisal
CONCLUSION
• This journal can be classifed as a VALID
journal
• IMPORTANCY in this journal were not
described well
• Result from the research in this journal is
APPLICABLE in Indonesia
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