TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination

Abstract

The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI.

Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration

“…It was also found that Cx3cr1, Trem2, Tyrobp, Cd33, Sall1, Tmem119, Siglec-H, Iba1, and P2ry12 specifically expressed in mouse microglia (Chiu et al, 2013;Galatro et al, 2017). Recently, another microglia specific marker Tmem119 has been identified as a marker of mature microglia in the brain (Bennett et al, 2016;Satoh et al, 2016;Bohnert et al, 2020) and Siglec-H expression specific to activated microglia where it cause phagocytosis of glioma cells of brain tumor (Kopatz et al, 2013;Konishi et al, 2017) and Olfml3 as a new Tgf-β1/Smad2 target gene in microglia (Neidert et al, 2018) has been reported. However, detailed studies on targeting these identified genes to understand microglia function in the regulation of oxidative stress and neurodegeneration are still elusive.…”

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

“…As already mentioned in previous publications, a special role as a stimulus of the resident microglia was attributed to the released myelin after damage of the myelin sheath with subsequent activation [ 57 , 58 ]. In addition to a very early response of microglia after TBI, one of our own publications also showed activation of the so-called M2 microglia/macrophages, which contribute to the regeneration of injured brain tissue through their phagocytic activity [ 19 ]. Demyelination, such as after TBI, results in an increased release of lipid components such as phospholipids and cholesterol, which are major constituents of myelin and are phagocytosed.…”

“…In addition to forensic neuropathological diagnostic methods, Benjamin Ondruschka and Michael Bohnert contributed equally to this work. postmortem biochemical analyses of various cytokines, acute phase proteins, CNS biomarkers [7,[13][14][15][16][17], or Na + -glucose transporters [18] in CSF and brain tissue as well as investigations of the early tissue reaction of local microglia after trauma are meanwhile increasingly performed [19]. Furthermore, the applicability of immunocytochemical staining in postmortem CSF could be demonstrated [20].…”

“…Currently, autopsy and histological examination of the traumatized tissue [ 12 ] are the main investigations used in the forensic postmortem routine to evaluate lethality and survival time (wound age). In addition to forensic neuropathological diagnostic methods, postmortem biochemical analyses of various cytokines, acute phase proteins, CNS biomarkers [ 7 , 13 – 17 ], or Na + -glucose transporters [ 18 ] in CSF and brain tissue as well as investigations of the early tissue reaction of local microglia after trauma are meanwhile increasingly performed [ 19 ]. Furthermore, the applicability of immunocytochemical staining in postmortem CSF could be demonstrated [ 20 ].…”

Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet–Induced Inflammation

“…Microglia simultaneously express several hallmarks, such as Iba1, Cx3cr1, P2ry12, Tmem119, Trem2, Cd11b, Hexb, Csf1r, Itgam, and Siglec , among others [ 38 , 39 , 40 , 41 , 42 , 43 ]. However, there is no unique expression pattern of these transcripts in these cells, that is, it varies according to the pathological condition, age, sex, species, and brain area [ 27 ].…”