Neuroprotection after hemorrhagic stroke depends on cerebral heme oxygenase-1

Kaiser S, Frase S, Selzner L, Lieberum JL, Wollborn J, Niesen WD, Foit NA, Heiland DH, Schallner N (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Antioxidants MDPI AG

Book Volume: 8

Article Number: 496

Journal Issue: 10

DOI: 10.3390/antiox8100496

Abstract

(1) Background: A detailed understanding of the pathophysiology of hemorrhagic stroke is still missing. We hypothesized that expression of heme oxygenase-1 (HO-1) in microglia functions as a protective signaling pathway. (2) Methods: Hippocampal HT22 neuronal cells were exposed to heme-containing blood components and cell death was determined. We evaluated HO-1-induction and cytokine release by wildtype compared to tissue-specific HO-1-deficient (LyzM-Cre.Hmox1fl/fl) primary microglia (PMG). In a study involving 46 patients with subarachnoid hemorrhage (SAH), relative HO-1 mRNA level in the cerebrospinal fluid were correlated with hematoma size and functional outcome. (3) Results: Neuronal cell death was induced by exposure to whole blood and hemoglobin. HO-1 was induced in microglia following blood exposure. Neuronal cells were protected from cell death by microglia cell medium conditioned with blood. This was associated with a HO-1-dependent increase in monocyte chemotactic protein-1 (MCP-1) production. HO-1 mRNA level in the cerebrospinal fluid of SAH-patients correlated positively with hematoma size. High HO-1 mRNA level in relation to hematoma size were associated with improved functional outcome at hospital discharge. (4) Conclusions: Microglial HO-1 induction with endogenous CO production functions as a crucial signaling pathway in blood-induced inflammation, determining microglial MCP-1 production and the extent of neuronal cell death. These results give further insight into the pathophysiology of neuronal damage after SAH and the function of HO-1 in humans.

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE)

How to cite

APA:

Kaiser, S., Frase, S., Selzner, L., Lieberum, J.L., Wollborn, J., Niesen, W.D.,... Schallner, N. (2019). Neuroprotection after hemorrhagic stroke depends on cerebral heme oxygenase-1. Antioxidants, 8(10). https://doi.org/10.3390/antiox8100496

MLA:

Kaiser, Sandra, et al. "Neuroprotection after hemorrhagic stroke depends on cerebral heme oxygenase-1." Antioxidants 8.10 (2019).

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