Abstract TMP120: Brain Plasticity Modulator P75 Neurotrophin Receptor And Its Mechanistically Linked Signaling Molecules Predict Clinical Outcome Across Different Acute Brain Injuries

Introduction: Brain plasticity and synaptic regeneration are important processes in recovering after acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). p75 neurotrophic receptor (p75NTR) is a consequential receptor modulating brain plasticity and apoptosis. Hypotheses: Measurable changes in serum levels of p75NTR mechanistically linked proteins are associated to recovery of acute brain injuries. Differentially expressed (DE) miRNAs after acute brain injuries target to p75NTR pathway and have association to outcome. Methods: Concentrations of p75NTR, NGF, sortilin, IL1β, TNFα and cyclophilin were measured from serum using ELISA. Prospective cohort (n=75) consisted of IS (n=30), aSAH (n=31) and TBI (n=14) patients. Serum samples were collected 24-48h after insults. Late samples (120-192h) were also taken from 12 aSAH patients. Outcome was measured 90 days after injury (mRS favorable 0-4, unfavorable 5-6). We generated characteristic curves and area under the curve (AUC) for weighted linear combination of the biomarkers with a linear discriminant analysis. MiRNAs were extracted from the cohort (early and late samples, n=53). Results: In the whole cohort (n=75) combination of cyclophilin, IL1β, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.69, p=0.01). In IS group combination of cyclophilin, sortilin, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.84, p=0.02). In aSAH group combination of IL1β, p75NTR and NGF predicted unfavorable mRS (AUC 0.77, p=0.07). In 12 aSAH patient sub-group (late samples included) combination of cyclophilin, IL1β, sortilin, p75NTR and TNFα predicted unfavorable mRS (AUC 1.0, p=0.07). In TBI group combination of cyclophilin, IL1β, p75NTR, NGF and TNFα predicted unfavorable mRS (AUC 0.79, p=0.08). In the aSAH group 2 DE miRNAs were detected, 4 in the IS group and 7 in the TBI group (p<0.05, FDR corrected). MiRNAs targeted p75NTR , NGF , IL1 β , cyclophilin ( PPIA ), and sortilin ( SORT1 ). Conclusions: p75NTR and mechanistically linked proteins predict outcome across different types of brain injuries suggesting a common mechanism irrespective of the type of brain insult. Identified DE miRNAs targeted studied molecules.