Phagocytosis of erythrocytes in the subarachnoid space at spinal nerve exits

Krahn, V

doi:10.1007/bf00215711

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…To date, it is controversially discussed if erythrophages and siderophages are exclusively generated in the CSF of patients with subarachnoid bleeding. It has been reported that blood contamination of the CSF as consequence of a previous lumbar puncture might induce the development of siderophages (27). Furthermore, it has been supposed that in some cases erythrophages might develop in vitro in the CSF in the presence of artificial blood contamination being not specific for a subarachnoid bleeding (12).…”

Section: Discussionmentioning

confidence: 99%

The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics

et al. 2019

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Background: Blood contamination due to traumatic lumbar puncture presents a diagnostic pitfall in cerebrospinal fluid (CSF) analysis. It is controversially discussed if phagocytosis of erythrocytes which can be found in the CSF after subarachnoid hemorrhage can also develop in vitro in the presence of artificial blood contamination. Furthermore, there is no consensus about the acceptable amount of artificial blood contamination on CSF protein results. Methods: Two measurement series were performed in order to investigate the role of artificial blood contamination on the possible development of erythrophages and siderophages in the CSF: (1) blood contamination was simulated in vitro by adding blood into the CSF. (2) CSF was investigated when blood contamination occurred during a traumatic lumbar puncture. In both types of experiments, CSF including blood was incubated for 24 h and for 72 h at room temperature or at 4°C. In the third measurement series, the effects of artificial blood contamination on CSF protein results were investigated. Blood contamination was simulated in vitro by adding different amounts of blood ending up with five different samples containing erythrocyte counts of 2,500, 5,000, 7,500, 10,000, and 20,000 per μl CSF. Results: Cytological examination revealed no evidence of erythrophages or siderophages in vitro . In contrast, already a low blood contamination (2,500 erythrocytes/μl CSF) led to false pathological results of total protein and albumin. Along with increasing amounts of blood, the frequency of false pathological protein results increased. A blood contamination of 5,000 erythrocytes/μl CSF resulted in a false positive intrathecal IgM production in nearly every fifth patient. In contrast, blood contamination with 5,000 erythrocytes/μl CSF was the acceptable amount of blood which did not lead to a false positive intrathecal synthesis of IgG and IgA. Conclusion: Erythrophages and siderophages do not develop in vitro . An extensive diagnostic work up for the source of blood in the CSF should be performed when erythrophages or siderophages are found in the CSF. The contamination of CSF with increasing volume of blood resulted in falsely elevated CSF protein concentrations. Hence, the amount of blood contamination has to be taken into consideration when interpreting CSF protein measurement results.

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Section: Discussionmentioning

confidence: 99%

The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics

et al. 2019

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“…More recently, the unique disease-driving function of hemoglobin post-aSAH was reinforced by a mouse model of prolonged intrathecal exposure to hemoglobin, which recapitulated the behavioral, vascular, cellular, and molecular changes seen after human aSAH. 28 Erythrophagocytes in the blood clot, which ingest decaying red blood cells and detoxify heme 29 and may exit the CNS via spinal nerve roots, 30 develop from CNS-resident meningeal and perivascular macrophages 31 and CSF/blood-derived monocytes, 32 but microglia may also participate in the process 33 if there is parenchymal extension of the hemorrhage. However, erythrophagocytosis is unable to clear large blood clots, especially since the CNS is an immune-privileged site with few resident myeloid cells and highly regulated monocyte influx.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation

Galea,

Bandyopadhyay,

Bulters

et al. 2023

Stroke

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Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

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Phagocytosis of erythrocytes in the subarachnoid space at spinal nerve exits

Cited by 2 publications

References 7 publications

The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics

The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation

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