Pentoxifylline Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats: Possibly via Inhibiting TLR 4/NF-κB Signaling Pathway
Autor: | Ling-Yun Wu, Meng-Liang Zhou, Hua-Sheng Zhang, Xiang-Sheng Zhang, Chun-hua Hang, Da-yong Xia |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Subarachnoid hemorrhage Phosphodiesterase Inhibitors Pharmacology Biochemistry Neuroprotection Pentoxifylline Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience Random Allocation 0302 clinical medicine medicine Animals Phosphodiesterase inhibitor business.industry NF-kappa B General Medicine Subarachnoid Hemorrhage medicine.disease Rats Toll-Like Receptor 4 030104 developmental biology Apoptosis Brain Injuries Immunology TLR4 Tumor necrosis factor alpha business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
Zdroj: | Neurochemical research. 42(4) |
ISSN: | 1573-6903 |
Popis: | Early brain injury (EBI) after subarachnoid hemorrhage (SAH) generally causes significant and lasting damage. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, has shown anti-inflammatory and neuroprotective properties in several brain injury models, but the role of PTX with respect to EBI following SAH remains uncertain. The purpose of this study was to investigate the effects of PTX on EBI after SAH in rats. Adult male Sprauge–Dawley rats were randomly assigned to the sham and SAH groups. PTX (30 or 60 mg/kg) or an equal volume of the administration vehicle (normal saline) was administrated at 30 min intervals following SAH. Neurological scores, brain edema, and neural cell apoptosis were evaluated. In order to explore other mechanisms, changes in the toll-like receptor 4 (TLR4) and the nuclear factor-κB (NF-κB) signaling pathway, in terms of the levels of apoptosis-associated proteins, were also investigated. We found that administration of PTX (60 mg/kg) notably improved neurological function and decreased brain edema at both 24 and 72 h following SAH. Treatment with PTX (60 mg/kg) significantly inhibited the protein expressions of TLR4, NF-κB, MyD88 and the downstream pro-inflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). PTX also significantly reduced neural cell death and BBB permeability. Our observations may be the first time that PTX has been shown to play a neuroprotective role in EBI after SAH, potentially by suppressing the TLR4/NF-κB inflammation-related pathway in the rat brain. |
Databáze: | OpenAIRE |
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