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.