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Abstract Background Cerebral edema (CE) at admission is a surrogate marker of ‘early brain injury’ (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH. Methods Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0–4 ‘subarachnoid hemorrhage early brain edema score’ (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3–5 days [T3] and 6–8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2). Results Of the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002–1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE. Conclusions We identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH. 

Ischemic stroke is a serious cerebrovascular event that results in cell death, blood-brain barrier dysfunction, tissue degradation, and inflammation, often leading to permanent disability or death. As the incidence of ischemic stroke continues to rise globally, it is crucial to examine the mechanisms of the various proteins and molecules contributing to worsened patient outcome and recovery. Cathepsin L, a cysteine protease known for degrading tissues in lysosomes and elsewhere, may play a role in brain tissue loss and inflammation after stroke. Studies have suggested that cathepsin L appears in the ischemic core shortly after stroke is induced. Using immunohistochemical staining, mass spectrometry, and other assays, the increase of cathepsin L in the brain was correlated with extracellular matrix and perlecan degradation after ischemic stroke. Additionally, injection of a cathepsin L inhibitor significantly reduced brain infarct size and improved functional scores. More research is needed to elucidate cathepsin L's role in post-stroke inflammation and brain damage, in order to further explore the factors contributing to worsened patient outcome after ischemic stroke and work toward finding better therapeutic interventions.