AUTHOR=Neumaier Felix , Stoppe Christian , Stoykova Anzhela , Weiss Miriam , Veldeman Michael , Höllig Anke , Hamou Hussam Aldin , Temel Yasin , Conzen Catharina , Schmidt Tobias Philip , Dogan Rabia , Wiesmann Martin , Clusmann Hans , Schubert Gerrit Alexander , Haeren Roel Hubert Louis , Albanna Walid 

TITLE=Elevated concentrations of macrophage migration inhibitory factor in serum and cerebral microdialysate are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1066724

DOI=10.3389/fneur.2022.1066724

ISSN=1664-2295

ABSTRACT=<sec><title>Objective</title><p>Inflammation is increasingly recognized to be involved in the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH) and may increase the susceptibility to delayed cerebral ischemia (DCI). Macrophage migration inhibitory factor (MIF) has been shown to be elevated in serum and cerebrospinal fluid (CSF) after aSAH. Here, we determined MIF levels in serum, CSF and cerebral microdialysate (MD) at different time-points after aSAH and evaluated their clinical implications.</p></sec><sec><title>Methods</title><p>MIF levels were measured in serum, CSF and MD obtained from 30 aSAH patients during early (EP<sub>d1−4</sub>), critical (CP<sub>d5−15</sub>) and late (LP<sub>d16−21</sub>) phase after hemorrhage. For subgroup analyses, patients were stratified based on demographic and clinical data.</p></sec><sec><title>Results</title><p>MIF levels in serum increased during CP<sub>d5−15</sub> and decreased again during LP<sub>d16−21</sub>, while CSF levels showed little changes over time. MD levels peaked during EP<sub>d1−4</sub>, decreased during CP<sub>d5−15</sub> and increased again during LP<sub>d16−21</sub>. Subgroup analyses revealed significantly higher serum levels in patients with aneurysms located in the anterior <italic>vs</italic>. posterior circulation during CP<sub>d5−15</sub> (17.3 [15.1–21.1] <italic>vs</italic>. 10.0 [8.4–11.5] ng/ml, <italic>p</italic> = 0.009) and in patients with DCI <italic>vs</italic>. no DCI during CP<sub>d5−15</sub> (17.9 [15.1–22.7] <italic>vs</italic>. 11.9 [8.9–15.9] ng/ml, <italic>p</italic> = 0.026) and LP<sub>d16−21</sub> (17.4 [11.7–27.9] <italic>vs</italic>. 11.3 [9.2–12.2] ng/ml, <italic>p</italic> = 0.021). In addition, MIF levels in MD during CP<sub>d5−15</sub> were significantly higher in patients with DCI <italic>vs</italic>. no DCI (3.6 [1.8–10.7] <italic>vs</italic>. 0.2 [0.1–0.7] ng/ml, <italic>p</italic> = 0.026), while CSF levels during the whole observation period were similar in all subgroups.</p></sec><sec><title>Conclusion</title><p>Our findings in a small cohort of aSAH patients provide preliminary data on systemic, global cerebral and local cerebral MIF levels after aSAH and their clinical implications.</p></sec><sec><title>Clinical trial registration</title><p><ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, identifier: NCT02142166.</p></sec>