Combined Phloretin and Human Platelet-rich Plasma Effectively Preserved Integrities of Brain Structure and Neurological Function in Rat after Traumatic Brain Damage

Kun-Chen Lin, Kuan-Hung Chen, Pei-Lin Shao, Han-Tan Chai, Pei-Hsun Sung, John Y Chiang, Sheung-Fat Ko, Hon-Kan Yip
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Abstract

Background: This study investigates whether phloretin, a brain-edema inhibitor, can enhance the therapeutic effects of human-derived platelet-rich plasma (hPRP) in reducing brain hemorrhagic volume (BHV) and preserving neurological function in rodents following acute traumatic brain damage (TBD)

Methods: Forty rats were divided into five groups: sham-control, TBD, TBD + phloretin (80 mg/kg/dose intraperitoneally at 30 minutes and on days 2/3 post-TBD), TBD + hPRP (80μL by left intra-carotid-artery injection at 3 hours post-TBD), and TBD + phloretin + hPRP. Cerebral tissues were harvested on day 28 post-TBD for analysis.

Results: Brain MRI on day 28 showed the lowest BHV in the sham-control group and the highest in the TBD group. BHV was significantly lower in the phloretin + hPRP group compared to the phloretin or hPRP alone groups, which had similar BHV. Neurological function followed an inverse pattern to BHV. By day 28, protein levels of upstream (HGMB1, TLR-2, TLR-4, MyD88, Mal, TRAM, TRIF, TRAF6, IKK-α, IKK-ß, p-NF-κB) and downstream (IL-1ß, TNF-α, iNOS) inflammation signalings, apoptosis (caspase3, PARP), and fibrosis (Smad3, TGF-ß) biomarkers, as well as flow cytometric assessment of inflammatory cells (CD11b/c+, Ly6G+, PMO+) and early (AN-V+/PI-) and late (AN-V+/PI+) mononuclear-cell apoptosis, displayed patterns similar to BHV. The number of inflammatory (CD68+, MMP9+) and brain-swelling/myelin-damaged (AQP4+, GFAP+) mediators also followed this pattern, while neuronal-myelin (Doublecortin+, NeuN, nestin) mediators showed an inverse relationship with BHV (all p<0.0001).

Conclusion: Combined phloretin and hPRP therapy is superior to either treatment alone in protecting the brain against TBD, primarily by suppressing inflammatory signaling and brain-swelling biomarkers.

联合使用毛果芸香素和人血小板丰富血浆可有效保护创伤性脑损伤后大鼠脑结构和神经功能的完整性
研究背景本研究测试了phloretin(一种脑水肿抑制剂)是否能增强人源血小板丰富血浆(hPRP)对急性创伤性脑损伤(TBD)后啮齿类动物减轻脑出血体积(BHV)和保护神经功能的治疗作用:方法:将大鼠(n=40)分为第1组(假对照)、第2组(TBD)、第3组[TBD + phloretin(80mg/kg/dose,30分钟腹腔注射,第2/3天后TBD)、第4组(TBD + PRP/80μL,TBD后3小时左侧颈动脉内注射)和第5组(TBD + phloretin + hPRP),TBD后第28天采集脑组织:结果:第28天的脑MRI显示,第1组的BHV最低,第2组最高,第5组明显低于第3/4组,但第3/4组之间相似,而神经功能显示出各组间BHV的相反模式(所有p&amp;amp;lt;0.0001)。72 小时后,上游(HGMB1/TLR-2/TLR-4/MyD88/Mal/TRAM/TRIF/TRAF6/IKK-α/IKK-ß/p-NF-κB)和下游(IL-1ß/TNF-α/iNOS)炎症信号蛋白水平均有所下降、凋亡(caspase3/PARP)和纤维化(Smad3/TGF-ß)生物标志物以及炎症细胞(CD11b/c+//Ly6G+/PMO+)和早期(AN-V+/PI-)/晚期(AN-V+/PI+)单核细胞凋亡的流式细胞术评估显示,各组间BHV的作用方式相似(所有p&;amp;amp;lt;0.0001).炎症介质(CD68+/MMP9+)和脑肿胀/髓鞘损伤介质(AQP4+/ GFAP+)的细胞数量显示出相似的方式,而神经元-髓鞘介质(Doublecortin+/NeuN/nestin)在各组间显示出与 BHV 相反的方式(所有 p&amp;amp;lt;0.0001):结论:在保护大脑免受 TBD 侵袭方面,联合使用毛果芸香碱和 hPRP 方案的效果优于单一疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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