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  • 1
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    Abstract WP222: Temporally Differentially Expressed MikroRNAs In Serum Predict Recovery In Different Acute Brain Injuries
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. Suppl_1 ( 2023-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: Brain plasticity is important processes in recovering after different types of acute brain injuries such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS) and traumatic brain injury (TBI). Knowledge gaps still exist which miRNAs contribute to recovery of the acute brain injuries. Hypotheses: Temporally differentially expressed (DE) miRNAs after acute brain injuries may have association to outcome irrespective the type of the acute brain injury. MiRNAs that are DE across different type of brain injuries may reveal important conserved associations that can reflect important biological mechanisms and serve as a biomarker. Methods: Prospective cohort (n=24) consisted of IS (n=8), aSAH (n=8) and TBI (n=8) patients. Two serum samples were collected per patient (early 24-48h and late 120-192h after injury). Outcome was measured 90 days after injury (mRS favorable 0-3 (n=15), unfavorable 4-6 (n=9). MiRNAs were extracted from the samples (total n = 48 samples). Sequencing was performed and DESeq2 was used to identify DE miRNAs. The miRNA putative target genes were predicted with miRWalk. Normalized expression values of identified DE miRNAs were used and linear canonical discriminant analysis (LDA) was performed. Canonical scores were used to build combinatory biomarker with logistic modelling predicting outcome. Results: We identified 22 temporally DE miRNAs (p 〈 0.05) that were in common across all acute brain injury types when compared between favorable and unfavorable groups. From this pool miRWalk target analysis identified 4 miRNAs (hsa-miR-146b-3p, hsa-miR-485-3p, hsa-miR-5010-5p, hsa-miR-485-5p) that targeted to known plasticity mechanism. LDA of these four miRNAs resulted an equation with canonical scores: 0.636 x [hsa-miR-146b-3p] + 0.576 x [hsa-miR-485-3p] + 0.652 x [hsa-miR-5010-5p] + 0.372 x [hsa-miR-485-5p] . The receiver operating characteristic curve generated showed AUC = 94.1%, 95% CI = (0.849, 1.00), p = 0.016 Conclusions: Results show that combinatory biomarker of identified miRNAs perform well across different type of brain injuries. Validation in larger cohort is justified. Identified common miRNAs also provide new targets for mechanistical validation in disease models of TBI and stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.54.suppl_1.WP222
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 2
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    Table_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-5-31)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-5-31)
    Abstract: Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2022.888815
    DOI: 10.3389/fneur.2022.888815.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 3
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    A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-09-11)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-09-11)
    Abstract: P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR’s related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p  〈  0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-72061-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 4
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    High angular resolution diffusion-weighted imaging in mild traumatic brain injury
    Elsevier BV ; 2017
    In:  NeuroImage: Clinical Vol. 13 ( 2017), p. 174-180
    Details
    In: NeuroImage: Clinical, Elsevier BV, Vol. 13 ( 2017), p. 174-180
    Type of Medium: Online Resource
    ISSN: 2213-1582
    URL: Article
    DOI: 10.1016/j.nicl.2016.11.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2701571-3
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  • 5
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    Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam
    Wiley ; 2020
    In:  Acta Anaesthesiologica Scandinavica Vol. 64, No. 9 ( 2020-10), p. 1278-1286
    Details
    In: Acta Anaesthesiologica Scandinavica, Wiley, Vol. 64, No. 9 ( 2020-10), p. 1278-1286
    Abstract: Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH. Methods Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4 μg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20 mm Hg above the baseline. Results Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean ± SD) 1.20 ± 0.14, 1.17 ± 0.13 ( P  = .93), 1.14 ± 0.09 ( P  = .72) and 1.19 ± 0.18 ( P  = 1.0) and sROR% was 150.89 ± 84.37, 75.22 ± 27.75 ( P  = .08), 128.25 ± 58.35 ( P  = .84) and 104.82 ± 36.92 ( P  = .42) at baseline and during 0.7, 1.0 and 1.4 μg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0 μg/kg/h dexmedetomidine ( P  = .02). Conclusions Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.
    Type of Medium: Online Resource
    ISSN: 0001-5172 , 1399-6576
    URL: Issue
    URL: Article
    DOI: 10.1111/aas.v64.9
    DOI: 10.1111/aas.13663
    RVK:
    XA 11250
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 80002-8
    detail.hit.zdb_id: 2004319-3
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  • 6
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    Abstract TMP120: Brain Plasticity Modulator P75 Neurotrophin Receptor And Its Mechanistically Linked Signaling Molecules Predict Clinical Outcome Across Different Acute Brain Injuries
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. Suppl_1 ( 2022-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.53.suppl_1.TMP120
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
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    Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries—A Prospective Cohort Study
    MDPI AG ; 2024
    In:  Biomedicines Vol. 12, No. 1 ( 2024-01-05), p. 112-
    Details
    In: Biomedicines, MDPI AG, Vol. 12, No. 1 ( 2024-01-05), p. 112-
    Abstract: Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients’ outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53–89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83–65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p 〈 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines12010112
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
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  • 8
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    A genome-wide association study of outcome from traumatic brain injury
    Elsevier BV ; 2022
    In:  eBioMedicine Vol. 77 ( 2022-03), p. 103933-
    Details
    In: eBioMedicine, Elsevier BV, Vol. 77 ( 2022-03), p. 103933-
    Type of Medium: Online Resource
    ISSN: 2352-3964
    URL: Article
    DOI: 10.1016/j.ebiom.2022.103933
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2799017-5
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  • 9
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    Abstract P809: A Comprehensive P75 Neurotrophin Receptor Gene Network and Pathway Analyses Identifying New Target Genes for Stroke Recovery
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. Suppl_1 ( 2021-03)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Abstract: Introduction: Therapeutic interest into the neurotrophins resides in their ability to regulate the process of neuronal and synaptic regeneration following acute brain injuries such as intracerebral hemorrhage, subarachnoid hemorrhage and ischemic stroke. P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred. Methods: We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n=235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Results: Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p 〈 0.05, FDR corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. Discussion: This study provides the largest comprehensive gene and functional network library of p75NTR and incorporates current knowledge using a large dataset approach that increases the overall understanding of complex p75NTR networks. These results suggest both new possible target genes for further investigation in p75NTR research, while also validating previously conducted research. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in stroke. Future directions: We are currently sequencing miRNA libraries from ischemic and hemorrhagic stroke patients’ plasma with longitudinal plasma samples and clinical data. This data together with presented results will be used to test identified novel targets in p75NTR engineered models in order seek novel therapeutic strategies to increase recovery after stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.52.suppl_1.P809
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 10
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    Abstract TMP25: Common Molecular Biomarkers in Different Types of Acute Brain Injuries Predicting Outcome
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Acute brain injuries, including aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI), entail complex recovery processes involving brain plasticity and synaptic regeneration mechanisms. Exploring lipidomic profiles, microRNA expression, and metabolomic changes can yield insights into recovery mechanisms, unveil conserved molecular associations, and identify potential biomarkers. Hypotheses: We hypothesized that regardless of injury type, variations in lipidomic and metabolomic profiles, along with differentially expressed microRNAs, share common characteristics. These changes likely mirror essential biological mechanisms and may correlate with outcomes. Methods: We studied a prospective cohort of patients with IS, aSAH, and TBI (N=71). Serum samples were collected once, followed by comprehensive profiling: lipidomics (Lipidyzer™ Platform), metabolomics (Orbitrap Profiling), and microRNA sequencing (DESeq2). Results: Univariate analysis unveiled candidate molecules predictive of outcomes. Multivariate combinatory linear discriminant analysis (LDA) demonstrated significant prognostic potential for favorable outcomes. The LDA equation combining eight biomarkers was: -0.239[LPC17:0] - 1.125[TAG51:2:FA15:0] + [TAG51:2:FA18:1] + [D-glucuronic Acid] + 0.416[hsa-miR-146b-3p] + 0.082[hsa-miR-485-3p] + 0.433[hsa-miR-5010-5p] + 0.727[hsa-miR-485-5p] , effectively predicting favorable outcomes. The AUC was 95.8%, 95% CI (0.88 - 1.00), p-value 0.023, indicating strong discriminatory power of the combinatory biomarker (OR 8.7, 95% CI 1.35-56.9). Conclusion: Findings reveal a shared pattern of lipidomic, metabolomic, and microRNA changes across distinct acute brain injuries. This warrants further investigation and validation, offering prospects for biomarker development, mechanistic validation, and therapeutic interventions in brain recovery. These shared features underscore the importance of interdisciplinary research for targeted, personalized interventions in diverse acute brain injuries.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.TMP25
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 80381-9
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