Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury

Abstract

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.

Hypothalamic Protein Profiling from Mice Subjected to Social Defeat Stress

“…In this study, we also found upregulation of Myelin Basic Protein (MBP) and associated proteins in the brain following stress in accordance with previous studies. MBP has been associated with neuronal death and trauma and has been found to be increased in CSF of dogs post traumatic brain injury (Bohnert et al , 2021; Su et al , 2012).…”

Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS

“…CSF samples were immediately centrifuged at 5000 rpm for 5 min at 4 °C and cytospin preparations were stained with the antibody mentioned above using an adapted protocol for immunocytochemistry [ 13 ] and identical dilutions .…”

“…Since the CSF is permanently resorbed, interstitial fluid (ISF) influx carrying degenerated proteins and waste products from all parts of the central nervous system (CNS) replenish resorbed CSF [3]. Cellular, microbial, metabolic, and structural proteins are considered as biomarkers that act as surrogate markers of CNS neuropathology, e.g., after traumatization [4][5][6][7][8][9][10][11][12][13][14][15]. Research and diagnosis of enhanced CSF-cell density after inflammatory and tumor-related brain affliction have a long history [16][17][18].…”

“…Since that time, even though it can be downregulated in some contexts [ 24 ], it has served for the immunohistochemical demonstration of microglia response to fatal TBI [ 25 ] or intoxications [ 26 ]. In addition, modified histochemical protocols could detect microglia in postmortem CSF samples of cases with TBI [ 13 ].…”

Association between CpG island DNA methylation in the promoter region of RELN and positive and negative types of schizophrenia

“…When myelin fracture and disintegration occur in the central nervous system because of direct mechanical damage (namely primary brain injury, such as cerebral contusion or intracranial hematoma, or as the result of a brain tumor), the myelin component MBP is released into bodily fluids, thus causing secondary brain injury. 13 Studies have shown that serum MBP is a prognostic marker of brain injury. 14 Additionally, changes in blood MBP levels may reflect the degree of glial injury in the central nervous system; however, few clinical studies have investigated whether changes in MBP may be an index for the development of schizophrenia.…”