Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages

Züleyha Doğanyiğit; Serpil Taheri; Aslı Okan; Zeynep Yılmaz; Arda Kaan Üner; Enes Akyüz; Mehmet Memiş; Ecmel Mehmetbeyoğlu; Alina Arulsamy; Mohd. Farooq Shaikh

doi:10.5114/fn.2024.140788

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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3/2024
vol. 62

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abstract:

Original paper

Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages

Züleyha Doğanyiğit

¹

,

Serpil Taheri

^{2, 3}

,

Aslı Okan

¹

,

Zeynep Yılmaz

²

,

Arda Kaan Üner

⁴

,

Enes Akyüz

⁵

,

Mehmet Memiş

⁶

,

Ecmel Mehmetbeyoğlu

^{2, 3}

,

Alina Arulsamy

⁷

,

Mohd. Farooq Shaikh

⁸

Department of Histology-Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
Department of Biophysics, Faculty of International Medicine, University of Health Sciences, Istanbul, Turkey
Department of Molecular Biology and Genetics, Erciyes University, Kayseri, Turkey
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia
School of Dentistry and Medical Sciences, Charles Sturt University, Orange, NSW, Australia

Folia Neuropathol 2024; 62 (3): 277-292

DOI: https://doi.org/10.5114/fn.2024.140788

Online publish date: 2024/08/05

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Introduction:
Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country’s healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI.

Material and methods:
Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis.

Results:
Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI.

Conclusions:
The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.

keywords:

Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages

Züleyha Doğanyiğit 1 , Serpil Taheri 2, 3 , Aslı Okan 1 , Zeynep Yılmaz 2 , Arda Kaan Üner 4 , Enes Akyüz 5 , Mehmet Memiş 6 , Ecmel Mehmetbeyoğlu 2, 3 , Alina Arulsamy 7 , Mohd. Farooq Shaikh 8

inflammation, autophagy, peripheral tissue, neurotrauma, gender difference

Züleyha Doğanyiğit

¹

,

Serpil Taheri

^{2, 3}

,

Aslı Okan

¹

,

Zeynep Yılmaz

²

,

Arda Kaan Üner

⁴

,

Enes Akyüz

⁵

,

Mehmet Memiş

⁶

,

Ecmel Mehmetbeyoğlu

^{2, 3}

,

Alina Arulsamy

⁷

,

Mohd. Farooq Shaikh

⁸