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Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm

  • Experimental Research - Vascular
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

The exact underlying pathogenic mechanisms and effective preventive or therapeutic interventions for cerebral vasospasm remain obscure. The thioredoxin (Trx) system performs important functions in the central nervous system including neurotrophic and neuroprotective actions. There is no study directly investigating the effects of subarachnoid hemorrhage (SAH) induced cerebral vasospasm on the Trx system in the literature.

Methods

Sixteen male New Zealand rabbits were randomly divided into two groups of eight rabbits each: a control group and a SAH group. The control group, (n = 8) was a sham surgery group in which SAH was not induced. In the SAH group, (n = 8), the SAH protocol was used to induce cerebral vasospasm. The brain and brainstem were removed and each brainstem was cut coronally into two pieces: an anterior part that contains basilar artery and a dorsal part that contains brainstem tissue. The brainstem tissue thioredoxin-1(Trx1), thioredoxin-2 (Trx2), thioredoxin reductase (TrxR), thioredoxin reductase-1 (TrxR1), thioredoxin-interacting protein (TXNIP) levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde levels (MDA) and tumor necrosis factor alpha (TNF-alpha) levels were investigated for determining the oxidative-antioxidative status of the related brain tissues. Basilar artery segments were investigated for cross-sectional area and wall thickness measurements.

Results

SAH statistically significantly reduced the tissue levels of Trx1 (p < 0.01) and TrxR (p < 0.01). Trx2 levels were not significantly altered after SAH (p > 0.05). SAH significantly reduced the expression of TrxR1 (p < 0.01) and significantly increased the expression of TXNIP (p < 0.01) when compared with controls. TOS levels and MDA levels significantly increased after SAH (p < 0.01) and TAS levels significantly reduced after SAH (p < 0.01). TNF-alpha levels significantly increased after SAH (p < 0.01). SAH-induced cerebral vasospasm significantly (p < 0.05) increased the wall thickness and reduced the mean cross-sectional area of the basilar artery (p < 0.05).

Conclusions

The Trx system seems to be negatively affected by the simultaneously interrelated enzymatic alterations during cerebral vasospasm.

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Acknowledgments

This study was supported by Necmettin Erbakan University Scientific Research Projects Office (Project No: 131218018)

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Necmettin Erbakan University Meram Faculty of Medicine, 42500, Konya, Turkey

    B. Kaya, F. Erdi, F. Keskin, Y. Karatas & E. Kalkan

  2. Department of Medical Biochemistry, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    I. Kılınc

  3. Department of Medical Microbiology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    B. Feyzıoglu

  4. Department of Medical Pathology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    H. Esen

  5. Department of Public Health, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    M. Uyar

Authors
  1. B. Kaya
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  2. F. Erdi
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  3. I. Kılınc
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  4. F. Keskin
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  5. B. Feyzıoglu
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  6. H. Esen
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  7. Y. Karatas
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  8. M. Uyar
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  9. E. Kalkan
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Corresponding author

Correspondence to F. Erdi.

Additional information

Comment

This is an interesting research, conducted in an already well-described rabbit model of SAH, and compared to sham operated controls. The primary objective of the study is the quantification, in the brainstem tissue, of the levels of thioredoxin-related proteins Trx1, Trx2, TrxR, TrxR1, TXNIP 72 h after SAH. Because the authors attempted to correlate changes in these proteins with the occurrence of cerebral vasospasm, they have simultaneously quantitatively analyzed five cross-sectional basilar artery segments measuring its wall thickness. As a secondary endpoint, in order to determine the oxidative-antioxidative status of these brain areas, they have assessed quantitatively the levels of the oxidative stress proteins TOS, TAS, MAD, and TNF-alpha. The major problem with this research is establishing a link between these three aims. SAH induces a global brain dysfunction, at various levels, and different interrelated enzymatic systems are consequently altered. For this, it is a complex disease. It remains to be elucidated if the alterations in the Trx system are a direct consequence of vasospasm instead of being a part of the simultaneously interrelated synchronous dysfunction post SAH. The Trx system seems to be negatively affected from the alterations after SAH. Although it has complex neuroprotective, neurotropic, ROS scavenging, and signal transduction effects, the alterations of the Trx system during vasospasm merit further investigations.

Domenico d'Avella and Antonino Germanò

Padova and Messina, Italy

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Kaya, B., Erdi, F., Kılınc, I. et al. Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm. Acta Neurochir 157, 793–800 (2015). https://doi.org/10.1007/s00701-015-2390-z

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  • DOI: https://doi.org/10.1007/s00701-015-2390-z

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