Brain injury has been proposed as the major cause of the poor outcomes associated with intracerebral hemorrhage (ICH). Emerging evidence indicates that the nuclear receptor, peroxisome proliferator-activated receptor β/δ (PPAR-β/δ), plays a crucial role in the pathological process of central nervous impairment. The present study was undertaken to evaluate the protective effects of PPAR-β/δ activation using a selective PPAR-β/δ agonist, GW0742, against brain injury after ICH in a mouse model. ICH was induced by intravenous injection of collagenase into the right caudate putamen. To examine the protective effect of PPAR-β/δ activation against ICH-induced brain injury, mice were either intraperitoneally injected with GW0742 (3 mg/kg, body weight) or saline (control group) 30 min before inducing ICH. Behavioral dysfunction was evaluated 24 and 72 h after injury. Then, all mice were killed to assess hematoma volume, brain water content, and blood-brain barrier (BBB) permeability. TUNEL and Nissl staining were performed to quantify the brain injury. The expression of PPAR-β/δ, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, Bcl-2-related X-protein (Bax), and B-cell lymphoma 2 (Bcl-2) in the perihematomal area was examined by immunohistochemistry and western blotting analysis. Mice treated with GW0742 showed significantly less severe behavioral deficits compared to the control group, accompanied by increased expression of PPAR-β/δ and Bcl-2, and increased expression of IL-1β, TNF-α, and Bax decreased simultaneously in the GW0742-treated group. Furthermore, the GW0742-pretreated group showed significantly less brain edema and BBB leakage. Neuronal loss was attenuated, and the number of apoptotic neuronal cells in perihematomal tissues reduced, in the GW0742-pretreated group compared to the control group. However, the hematoma volume did not decrease significantly on day 3 after ICH. These results suggest that the activation of PPAR-β/δ exerts a neuroprotective effect on ICH-induced brain injury, possibly through anti-inflammatory and anti-apoptotic pathways.

中文翻译：

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在胶原酶诱导的脑出血小鼠模型中，PPAR-β/δ 的激活通过抑制炎症和细胞凋亡来减轻脑损伤。

脑损伤已被认为是与脑出血 (ICH) 相关的不良结果的主要原因。新出现的证据表明，核受体过氧化物酶体增殖物激活受体β/δ（PPAR-β/δ）在中枢神经损伤的病理过程中起着至关重要的作用。本研究旨在评估使用选择性 PPAR-β/δ 激动剂 GW0742 激活 PPAR-β/δ 对小鼠模型中 ICH 后脑损伤的保护作用。通过将胶原酶静脉注射到右侧尾状壳核中来诱导 ICH。为了检查 PPAR-β/δ 激活对 ICH 诱导的脑损伤的保护作用，在诱导 ICH 前 30 分钟，小鼠要么腹腔注射 GW0742（3 mg/kg，体重）或盐水（对照组）。在受伤后 24 和 72 小时评估行为功能障碍。然后，杀死所有小鼠以评估血肿体积、脑含水量和血脑屏障 (BBB) 通透性。进行 TUNEL 和 Nissl 染色以量化脑损伤。PPAR-β/δ、白细胞介素 (IL)-1β、肿瘤坏死因子 (TNF)-α、Bcl-2 相关 X 蛋白 (Bax) 和 B 细胞淋巴瘤 2 (Bcl-2) 在通过免疫组织化学和蛋白质印迹分析检查血肿周围区域。与对照组相比，GW0742 治疗的小鼠表现出明显较轻的行为缺陷，伴随着 PPAR-β/δ 和 Bcl-2 的表达增加，并且在 GW0742 中 IL-1β、TNF-α 和 Bax 的表达增加同时下降-治疗组。此外，GW0742 预处理组的脑水肿和 BBB 渗漏显着减少。与对照组相比，GW0742预处理组的神经元损失减弱，血肿周围组织中凋亡神经元细胞的数量减少。然而，ICH 后第 3 天血肿体积并未显着减少。这些结果表明，PPAR-β/δ 的激活可能通过抗炎和抗凋亡途径对 ICH 诱导的脑损伤发挥神经保护作用。