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J Stroke Cerebrovasc Dis. 2019 Oct 4:104375. doi: 10.1016/j.jstrokecerebrovasdis.2019.104375. [Epub ahead of print]

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway.

Author information

1
Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China.
2
Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, Fuzhou, Fujian China. Electronic address: unionnstu@hotmail.com.

Abstract

BACKGROUND:

Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI.

MATERIALS AND METHODS:

Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-κB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain were examined by ELISA.

RESULTS:

Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-κB p65, COX-2, TNF-α, and IL-1β, all of which were inhibited by LY294002.

CONCLUSION:

These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

KEYWORDS:

PI3K/Akt; Subarachnoid hemorrhage; early brain injury; inflammation; oxidative stress; propofol

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