Early NO-donor treatment improves acute perfusion deficit and brain damage after experimental subarachnoid hemorrhage in rats

Lilla, Nadine; Hartmann, Jasmin; Koehler, Stefan; Ernestus, Ralf‐Ingo; Westermaier, Thomas

doi:10.1016/j.jns.2016.09.032

Cited by 11 publications

(3 citation statements)

References 45 publications

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“…It was previously shown experimentally that NO application reverses microarteriolar constriction, 25 improves CBF, 26 and reduces the number of microvasospasms by >80%. As a result, brain damage and functional outcome improved.…”

Section: Discussionmentioning

confidence: 93%

Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage

Liu

Schwarting

Terpolilli

et al. 2021

Stroke

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Background and Purpose: Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia resulting in high acute mortality and severe chronic neurological deficits. Spasms of the pial and intraparenchymal microcirculation (microvasospasms) contribute to acute cerebral ischemia after SAH; however, the underlying mechanisms remain unknown. We hypothesize that free iron (Fe 3+ ) released from hemolytic red blood cells into the subarachnoid space may be involved in microvasospasms formation. Methods: Male C57BL/6 mice (n=8/group) received 200 mg/kg of the iron scavenger deferoxamine or vehicle intravenously and were then subjected to SAH by filament perforation. Microvasospasms of pial and intraparenchymal vessels were imaged three hours after SAH by in vivo 2-photon microscopy. Results: Microvasospasms occurred in all investigated vessel categories down to the capillary level. Deferoxamine significantly reduced the number of microvasospasms after experimental SAH. The effect was almost exclusively observed in larger pial arterioles (>30 µm) covered with blood. Conclusions: These results provide proof-of-principle evidence that Fe 3+ is involved in the formation of arteriolar microvasospasms after SAH and that arteriolar and capillary microvasospasms are triggered by different mechanisms. Deciphering the mechanisms of Fe 3+ -induced microvasospasms may result in novel therapeutic strategies for SAH patients.

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Section: Discussionmentioning

confidence: 93%

Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage

Liu

Schwarting

Terpolilli

et al. 2021

Stroke

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“…Together with histological findings adjacent to the hematoma, the perfusion-restricted tissue may further contribute to brain edema formation 47 but may also serve as a potential therapeutic target. 48 In fact, the pathogenesis of cytotoxic edema is controversially discussed since other researchers did not find a link between perilesional CBF restriction, blood pressure, and perilesional edema in patients. 49 The ovine ICH model may allow to resolve and clarify these issues in further studies.…”

Section: Discussionmentioning

confidence: 99%

Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage

Boltze

Ferrara

Hainsworth

et al. 2018

J Cereb Blood Flow Metab

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Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.

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“…For neurological examination the animal was placed into an uncovered cage. After a ten-minute acclimatization interval, activity was evaluated by following a previously described observational protocol 18. This protocol resembles a modification of the assessment of spontaneous activity reported by Garcia et al in the framework of a large-scale assessment protocol for evaluation of the neurological performance after experimental stroke 19…”

Section: Methodsmentioning

confidence: 99%

Early antiinflammatory therapy attenuates brain damage after sah in rats

Vadokas

Koehler

Weiland

et al. 2019

Translational Neuroscience

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Background Early inflammatory processes may play an important role in the development of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experimental studies suggest that anti-inflammatory and membrane-stabilizing drugs might have beneficial effects, although the underlying mechanisms are not fully understood. The aim of this study was to investigate the effect of early treatment with methylprednisolone and minocycline on cerebral perfusion and EBI after experimental SAH. Methods Male Sprague-Dawley rats were subjected to SAH using the endovascular filament model. 30 minutes after SAH, they were randomly assigned to receive an intravenous injection of methylprednisolone (16mg/kg body weight, n=10), minocycline (45mg/kg body weight, n=10) or saline (n=11). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (LCBF) over both hemispheres were recorded continuously for three hours following SAH. Neurological assessment was performed after 24 hours. Hippocampal damage was analyzed by immunohistochemical staining (caspase 3). Results Treatment with methylprednisolone or minocycline did not result in a significant improvement of MABP, ICP or LCBF. Animals of both treatment groups showed a non-significant trend to better neurological recovery compared to animals of the control group. Mortality was reduced and hippocampal damage significantly attenuated in both methylprednisolone and minocycline treated animals. Conclusion The results of this study suggest that inflammatory processes may play an important role in the pathophysiology of EBI after SAH. Early treatment with the anti-inflammatory drugs methylprednisolone or minocycline in the acute phase of SAH has the potential to reduce brain damage and exert a neuroprotective effect.

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Early NO-donor treatment improves acute perfusion deficit and brain damage after experimental subarachnoid hemorrhage in rats

Cited by 11 publications

References 45 publications

Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage

Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage

Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage

Early antiinflammatory therapy attenuates brain damage after sah in rats

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