(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.Hmox1 fl/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.
Transcranial direct current stimulation (tDCS) induces polaritydependent neuronal changes at both a structural and functional level [1, 2], ranging from transient changes in neuronal excitability to longer lasting ultrastructural alterations in synapse architecture [3, 4]. Neurons and their supplying vessels form a spatially and functionally related neurovascular unit [5], with neurovascular coupling referring to a local variability in cerebral blood flow (CBF) in response to neural metabolic demand [6, 7]. Regional CBF is altered by tDCS in humans [8-13] as well as in animal models [14-16]. Data on microvasculature on the single-vessel level via two-photon microscopy during and after anodal DCS in vivo at intensities and durations close to clinical protocols are not available.Neurovascular coupling relies on multidirectional signaling pathways between neurons, glia, and the surrounding vascular network.In the arteriolar vessel wall, contractile smooth muscle cells mediate vascular tone in response to signals from the neurovascular unit. In
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