Quantitative proteomic analysis of the aging brain after intracerebral hemorrhage

脑出血(ICH)是中风的一种破坏性亚型，目前尚无有效的治疗方法。缺乏 治疗方案的选择在一定程度上导致了对脑出血病理生理学的模糊认识。沿着这些路线，尽管 随着老年人脑出血患病率的增加，脑老化后发生的分子水平变化 Ich在很大程度上仍然是个谜。为了解决这一关键的知识差距，提出了两个具体目标。目标1： 目的：探讨增龄性脑出血后脑蛋白质组的变化。目的2：确定年龄诱导的 脑出血后小胶质细胞和脑浸润性单核细胞衍生巨噬细胞的蛋白水平变化。这个 建议的研究采用临床前脑出血模型，并包括无偏见和严格的蛋白质组学方法 例如无标记和TMT标记的质谱学和生物信息学方法。成功完成 该项目将寻找新的分子调节剂来改善脑出血后的神经预后 老年人。此外，这些研究将首次定义急性分离的小胶质细胞和 巨噬细胞，在脑出血后的脑损伤和修复中起关键作用的细胞。

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with no effective treatment. Lack of treatment options partly contributes to the poorly defined pathophysiology of ICH. Along these lines, despite the increasing prevalence of ICH in the elderly, the molecular level changes that occur in the aging brain after ICH remains largely enigmatic. To address this critical knowledge gap, two specific aims are proposed. Aim 1: To determine the age-induced changes in the brain proteome after ICH. Aim 2: To determine the age-induced protein level changes in microglia and brain-infiltrating monocyte-derived macrophages (BMDM) after ICH. The proposed studies employ a preclinical model of ICH and include unbiased and rigorous proteomics approaches such as label-free and TMT-labeling Mass spectrometry and bioinformatics approaches. Successful completion of the project would identify novel molecular regulators to improve the neurological outcomes after ICH in the elderly. Also, the studies would define, for the first time, the proteomic profile of acutely isolated microglia and macrophages, the cells that play key roles in brain damage and repair after ICH.