scholarly journals Increased Mitochondrial Dysfunction Associated with Autophagy and Mitophagy in Cerebrospinal Fluid Cells Following Subarachnoid Hemorrhage in Patients with Delayed Cerebral Ischemia

2021 ◽  
Author(s):  
Dong Hyuk Youn ◽  
Youngmi Kim ◽  
Bong Jun Kim ◽  
Myeong Seon Jeong ◽  
Jooeun Lee ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Mitochondrial Dysfunction ◽  
Delayed Cerebral Ischemia ◽  
Underlying Mechanism ◽  
Autophagic Flux ◽  
Immunogold Staining ◽  
Csf Cells ◽  
Insight Into

Abstract Decreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied with delayed cerebral ischemia (DCI); however, the underlying mechanism remains unclear. We evaluated the mitochondrial dysfunction associated with autophagy and mitophagy in CSF cells for possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n=21; and non-DCI, n=35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. DCI patients showed a significantly increased mRNA expression (2-ΔCt) than non-DCI patients: DAPK1, 0.279 (0.220–0.297) in DCI vs. 0.043 (0.021–0.086) in non-DCI; BNIP3L, 0.134 (0.060–0.202) in DCI vs. 0.045 (0.020–0.101) in non-DCI; and PINK1, 0.064 (0.044–0.810) in DCI vs. 0.045 (0.012–0.063) in non-DCI. Other markers including BAX, ULK1, and NDP52 did not differ significantly. The vWF-positive CSF cells showed a colocalization with antibodies for DAPK1, BNIP3L/NIX, PINK1, and BECN1 with dysfunctional mitochondria. Increased dysfunctional mitochondria associated with autophagy and mitophagy are closely associated with DCI pathogenesis.

scholarly journals Mitochondrial dysfunction associated with autophagy and mitophagy in cerebrospinal fluid cells of patients with delayed cerebral ischemia following subarachnoid hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Hyuk Youn ◽  
Youngmi Kim ◽  
Bong Jun Kim ◽  
Myeong Seon Jeong ◽  
Jooeun Lee ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Mitochondrial Dysfunction ◽  
Delayed Cerebral Ischemia ◽  
Multivariable Logistic Regression Analysis ◽  
Autophagic Flux ◽  
Immunogold Staining ◽  
Csf Cells ◽  
Insight Into

AbstractDecreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied by delayed cerebral ischemia (DCI). However, whether abnormal mechanisms of mitochondria are associated with the development of DCI has not been reported yet. Under cerebral ischemia, mitochondria can transfer into the extracellular space. Mitochondrial dysfunction can aggravate neurologic complications. The objective of this study was to evaluate whether mitochondrial dysfunction might be associated with autophagy and mitophagy in CSF cells to provide possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n = 21; and non-DCI, n = 35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. Compared to non-DCI patients, DCI patients showed significantly increased mRNA expression levels (2−ΔCt) of DAPK1, BNIP3L, and PINK1, but not BAX, ULK1, or NDP52. Multivariable logistic regression analysis revealed that Hunt and Hess grade ≥ IV (p = 0.023), DAPK1 (p = 0.003), and BNIP3L (p = 0.039) were related to DCI. Increased mitochondrial dysfunction associated with autophagy and mitophagy could play an important role in DCI pathogenesis.

scholarly journals Cerebrospinal Fluid 20-HETE Is Associated With Delayed Cerebral Ischemia and Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2011 ◽  
Vol 42 (7) ◽  
pp. 1872-1877 ◽  
Author(s):  
Elizabeth A. Crago ◽  
Bhavani P. Thampatty ◽  
Paula R. Sherwood ◽  
Chie-Wen J. Kuo ◽  
Catherine Bender ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Poor Outcomes

scholarly journals Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sami Ridwan ◽  
Alexander Grote ◽  
Matthias Simon
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Interleukin 6 ◽  
Time Course ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Interindividual Variations ◽  
Potential Biomarker ◽  
Diagnostic Usefulness

AbstractInterleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

Increased CSF neopterin levels in subarachnoid hemorrhage

1990 ◽  
Vol 73 (1) ◽  
pp. 69-71 ◽  
Author(s):  
Tiit Mathiesen ◽  
Dietmar Fuchs ◽  
Helmut Wachter ◽  
Hans von Holst
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
T Cell ◽  
Cerebral Ischemia ◽  
T Cell Activation ◽  
Macrophage Activation ◽  
Cell Activation ◽  
Delayed Cerebral Ischemia ◽  
Content Type ◽  
Fine Print

✓ Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH.

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