Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid
The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numero...
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Mary Ann Liebert
2024-11-01
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| Series: | Neurotrauma Reports |
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| Online Access: | https://www.liebertpub.com/doi/10.1089/neur.2024.0050 |
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| author | Philip Dyhrfort Caroline Lindblad Anna Widgren Johan Virhammar Fredrik Piehl Jonas Bergquist Faiez Al Nimer Elham Rostami |
| author_facet | Philip Dyhrfort Caroline Lindblad Anna Widgren Johan Virhammar Fredrik Piehl Jonas Bergquist Faiez Al Nimer Elham Rostami |
| author_sort | Philip Dyhrfort |
| collection | DOAJ |
| description | The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 46 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from n = 12 patients with acute TBI. The resulting protein findings were then compared with CSF obtained by lumbar puncture from n = 14 patients with noninfectious CNS disorders comprising relapsing–remitting multiple sclerosis, anti-N-methyl-d-aspartate-receptor encephalitis, acute disseminated encephalomyelitis, and n = 13 patients with progressive multifocal leukoencephalopathy, herpes simplex encephalitis, and other types of viral meningitis. We also utilized n = 7 healthy controls (HC). In the comparison between TBI and noninfectious inflammatory CNS disorders, concentrations of 57 proteins significantly differed between the groups. Among them, 20 and 37 proteins were up- and downregulated, respectively. No proteins were uniquely identified in the TBI group. In the comparison of TBI and HC, 55 proteins were significantly different, with 24 and 31 proteins being up- and downregulated, respectively. Four proteins were uniquely identified in the TBI group, (FGG, HBA1, TKT, CA1). In the TBI versus infectious inflammatory CNS disorders, 57 proteins differed significantly between the groups, with 17 and 40 proteins being up- and downregulated, respectively. No proteins were uniquely identified in the TBI group. Due to large discrepancies between the groups compared, the following proteins were selected for further deeper analysis among those being differentially regulated: APOE, CFB, CHGA, CHI3L1, C3, FCGBP, FGA, GSN, IGFBP7, SERPINA3, SOD3, and TTR. We found distinct proteomic profiles in the CSF of TBI patients compared with HC and different disease controls, indicating a specific interplay between inflammatory factors, metabolic response, and cell integrity. In relation to primarily infectious or inflammatory disorders, unique inflammatory pathways seem to be engaged, and could potentially serve as future treatment targets. |
| format | Article |
| id | doaj-art-974c994c4e93479eac90e2b92fa606a7 |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-11-01 |
| publisher | Mary Ann Liebert |
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| series | Neurotrauma Reports |
| spelling | doaj-art-974c994c4e93479eac90e2b92fa606a72025-08-20T03:24:55ZengMary Ann LiebertNeurotrauma Reports2689-288X2024-11-015185787210.1089/neur.2024.0050Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal FluidPhilip Dyhrfort0Caroline Lindblad1Anna Widgren2Johan Virhammar3Fredrik Piehl4Jonas Bergquist5Faiez Al Nimer6Elham Rostami7Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Chemistry—BMC, Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.Department of Chemistry—BMC, Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, Sweden.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.Department of Medical Sciences, Uppsala University, Uppsala, Sweden.The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 46 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from n = 12 patients with acute TBI. The resulting protein findings were then compared with CSF obtained by lumbar puncture from n = 14 patients with noninfectious CNS disorders comprising relapsing–remitting multiple sclerosis, anti-N-methyl-d-aspartate-receptor encephalitis, acute disseminated encephalomyelitis, and n = 13 patients with progressive multifocal leukoencephalopathy, herpes simplex encephalitis, and other types of viral meningitis. We also utilized n = 7 healthy controls (HC). In the comparison between TBI and noninfectious inflammatory CNS disorders, concentrations of 57 proteins significantly differed between the groups. Among them, 20 and 37 proteins were up- and downregulated, respectively. No proteins were uniquely identified in the TBI group. In the comparison of TBI and HC, 55 proteins were significantly different, with 24 and 31 proteins being up- and downregulated, respectively. Four proteins were uniquely identified in the TBI group, (FGG, HBA1, TKT, CA1). In the TBI versus infectious inflammatory CNS disorders, 57 proteins differed significantly between the groups, with 17 and 40 proteins being up- and downregulated, respectively. No proteins were uniquely identified in the TBI group. Due to large discrepancies between the groups compared, the following proteins were selected for further deeper analysis among those being differentially regulated: APOE, CFB, CHGA, CHI3L1, C3, FCGBP, FGA, GSN, IGFBP7, SERPINA3, SOD3, and TTR. We found distinct proteomic profiles in the CSF of TBI patients compared with HC and different disease controls, indicating a specific interplay between inflammatory factors, metabolic response, and cell integrity. In relation to primarily infectious or inflammatory disorders, unique inflammatory pathways seem to be engaged, and could potentially serve as future treatment targets.https://www.liebertpub.com/doi/10.1089/neur.2024.0050central nervous systemencephalitisfluidic protein biomarkerhuman studiesinflammationmass-spectrometry |
| spellingShingle | Philip Dyhrfort Caroline Lindblad Anna Widgren Johan Virhammar Fredrik Piehl Jonas Bergquist Faiez Al Nimer Elham Rostami Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid Neurotrauma Reports central nervous system encephalitis fluidic protein biomarker human studies inflammation mass-spectrometry |
| title | Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid |
| title_full | Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid |
| title_fullStr | Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid |
| title_full_unstemmed | Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid |
| title_short | Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid |
| title_sort | deciphering proteomic expression in inflammatory disorders a mass spectrometry exploration comparing infectious noninfectious and traumatic brain injuries in human cerebrospinal fluid |
| topic | central nervous system encephalitis fluidic protein biomarker human studies inflammation mass-spectrometry |
| url | https://www.liebertpub.com/doi/10.1089/neur.2024.0050 |
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