Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications

Bohnert, Simone; Georgiades, Kosmas; Monoranu, Camelia‐Maria; Bohnert, Michael; Büttner, Andreas; Ondruschka, Benjamin

doi:10.1007/s00414-021-02699-5

Cited by 8 publications

(4 citation statements)

References 35 publications

(43 reference statements)

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“…In 2016, TMEM119, a trans-membranous molecule, proved to be a specific and robust microglial marker [ 7 ]. Since that time, it has served for the immunohistochemical demonstration of microglial response to fatal traumatic brain injury (TBI) or intoxication [ 8 , 9 ]. In addition, the assessment of the density of TMEM119-positive microglial cell profiles in cytospin preparations of the CSF after different fatalities and postmortem intervals (PMI) could be used as a marker for the evaluation of complex neuropathological processes in the CNS [ 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Multiorgan immunohistochemical endothelial expression of E-selectin in a forensic case of sepsis

Bohnert

Trella

Preiß

et al. 2023

Forensic Sci Med Pathol

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Sepsis is one of the major threats for the survival and prognosis of patients in intensive care units. In cases where detailed clinical data and monitoring is available, the diagnosis of sepsis is reliable. But when clinical data are incomplete or missing and sepsis is only suspected based on the autopsy results, the picture is often equivocal. This report describes the gross pathological findings obtained from the autopsy of a 48-year-old woman with Crohn’s disease after surgical intervention. Macroscopically, we found intestinal perforation and signs of peritonitis. Histologically, the pulmonary/bronchial arteries were lined with E-selectin (CD 62E)-positive endothelial cells, which are an established postmortem histological marker of sepsis. We extended our investigations to the cerebral cortex and subcortical medullary layer. The endothelium of the cortical vessels and those in the cerebral medullary layer were likewise immunopositive for E-selectin. Furthermore, numerous TMEM119-positive, highly ramified microglial cell profiles were found in the grey and white matter. Microglial cells were lining the vascular profiles. In addition, TMEM119-positive microglial profiles were abundant in the cerebrospinal fluid (CSF). Multiorgan E-selectin positivity of the vascular endothelia provides further evidence for the postmortem diagnosis of sepsis.

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Section: Discussionmentioning

confidence: 99%

Multiorgan immunohistochemical endothelial expression of E-selectin in a forensic case of sepsis

Bohnert

Trella

Preiß

et al. 2023

Forensic Sci Med Pathol

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“…The total area of the images comprised 5.8 mm 2 (1.16 mm 2 per single photograph). For quantitative evaluation of the sections, an image processing software (Leica LASX, Wetzlar, Germany) was used as described before [ 26 ]. Prior to digital image analysis, parameters of cell morphology (size of profiles and staining intensity) were defined for the TMEM119 antibody.…”

Section: Methodsmentioning

confidence: 99%

“…In 2016, TMEM119, a trans-membranous molecule [ 23 ], was proved to be a specific and robust microglial marker. 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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction.

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“…For example, a positron emission tomography study with the 18 kDa translocator protein radioligand [F- 18 ]FEPPA to evaluate microgliosis found no difference between METH abusers and controls [ 216 ]. Further, human brain tissue from death cases of lethal intoxications by METH found no difference in TMEM119 [ 217 ]. Thus, more studies are necessary to understand how METH abuse can alter microglia activity since microglial markers themselves could be affected by METH exposure.…”

Section: Responses Of Microglia To Psychostimulantsmentioning

confidence: 99%

Role of Microglia in Psychostimulant Addiction

Silva

Iglesias

Candelario‐Jalil

et al. 2023

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The use of psychostimulant drugs can modify brain function by inducing changes in the reward system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic pathway. However, the etiopathogenesis of addiction is a much more complex process. Previous data have suggested that microglia and other immune cells are involved in events associated with neuroplasticity and memory, which are phenomena that also occur in addiction. Nevertheless, how dependent is the development of addiction on the activity of these cells? Although the mechanisms are not known, some pathways may be involved. Recent data have shown psychoactive substances may act directly on immune cells, alter their functions and induce various inflammatory mediators that modulate synaptic activity. These could, in turn, be involved in the pathological alterations that occur in substance use disorder. Here, we extensively review the studies demonstrating how cocaine and amphetamines modulate microglial number, morphology, and function. We also describe the effect of these substances in the production of inflammatory mediators and a possible involvement of some molecular signaling pathways, such as the toll-like receptor 4. Although the literature in this field is scarce, this review compiles the knowledge on the neuroimmune axis that is involved in the pathogenesis of addiction, and suggests some pharmacological targets for the development of pharmacotherapy.

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Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications

Cited by 8 publications

References 35 publications

Multiorgan immunohistochemical endothelial expression of E-selectin in a forensic case of sepsis

Multiorgan immunohistochemical endothelial expression of E-selectin in a forensic case of sepsis

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

Role of Microglia in Psychostimulant Addiction

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