Abstract
Abstract INTRODUCTION ISO-alpha-acids (IAA) was reported to be useful for the prevention of dementia as a PPAR-gamma agonist in rats, but the application of IAA in intracerebral hemorrhage (ICH) was still limited. METHODS ICH models were built in Vivo and 90 SD rats were randomized to 5 groups: ICH + IAA intraperitoneal injection (IAA), ICH + normal saline intraperitoneal injection (control), ICH without any intraperitoneal injections (vehicle), Sham, and Mock. Neurological functions of rats, hematoma volume, and brain water content were evaluated 1-d, 3-d, and 7-d postoperation. Microglia of SD rats were sub cultured in Vitro. According to different interventions, 4 groups were set, including IAA, PPAR-gamma antagonist, normal saline (control), and normal cultured (vehicle). Western blotting, immunofluorescence, flow cytometry, and RT-PCR were used to detect the expression of molecular markers, proteins and mRNAs. RESULTS In ICH rats, intraperitoneal injection of IAA was able to promote hematoma clearance, to relieve brain water content and improve neurological functions. Detected by western blot, immunofluorescence, flow cytometry, and reverse transcription polymerase chain reaction (RT-PCR), IAA was able to significantly increase the expression of CD36, CD11b, and CD206, and inhibit the expression of CD80, CD86, TLR4, NF-kappaB, TNF-alpha, and IL-1beta comparing with other groups (P < .05) in Vivo and Vitro. IAA was able to significantly increase both in CD11b and CD206 double-positive anti-inflammatory type microglia and in microglia phagocytosis in the brain (P < .05). CONCLUSION IAA induces microglia to M2 type, characterized by phagocytosis and anti-inflammation, via activating PPAR-gamma signaling pathway in Vivo and Vitro. In ICH rats, administration of IAA is able to facilitate intracerebral hematoma absorption, alleviate brain edema, suppress inflammatory reactions, protect neurological functions, and finally improve rat's outcome.
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