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• Neuroinflammation induces activation of endothelial cells in the nervous system. • Particles targeting activated endothelial cells indirectly reveal neuroinflammation. • Micro-sized particles of iron oxide allow ultra-sensitive molecular MRI. • Biocompatible micro-sized particles are awaited for clinical translation. The ability to detect a molecular target in the central nervous system non-invasively and at high spatial resolution using magnetic resonance imaging (MRI) has attracted the interest of researchers for several decades. Yet, molecular MRI studies remain restricted to the preclinical stage and the path to clinical translation remains unclear. The focus of molecular MRI of neuroinflammation has moved from parenchymal to vascular targets, that are more easily reachable by intravenously injected probes. This has allowed the use of large superparamagnetic probes, such as micro-sized particles of iron oxide (MPIO), that dramatically improved the sensitivity of molecular MRI compared to smaller contrast agents. In particular, recent studies demonstrated the feasibility of unraveling inflammation in the brain by MRI using MPIO able to bind activated endothelial cells with potential applications in neurovascular, neuroinflammatory and neurodegenerative disorders. In the present review, we present the most striking advances in the field and the remaining challenges that must be overcome before clinical use of molecular MRI of neuroinflammation. [ABSTRACT FROM AUTHOR]

Although recent technical advances in thrombectomy have revolutionised acute stroke treatment, prevalence of disability and death related to stroke remain high. Therefore, plasminogen activators-eukaryotic, bacterial, or engineered forms that can promote fibrinolysis by converting plasminogen into active plasmin and facilitate clot breakdown-are still commonly used in the acute treatment of ischaemic stroke. Hence, plasminogen activators have become a crucial area for clinical investigation for their ability to recanalise occluded arteries in ischaemic stroke and to accelerate haematoma clearance in haemorrhagic stroke. However, inconsistent results, insufficient evidence of efficacy, or reports of side-effects in trial settings might reduce the use of plasminogen activators in clinical practice. Additionally, the mechanism of action for plasminogen activators could extend beyond the vessel lumen and involve plasminogen-independent processes, which would suggest that plasminogen activators have also non-fibrinolytic roles. Understanding the complex mechanisms of action of plasminogen activators can guide future directions for therapeutic interventions in patients with stroke. [ABSTRACT FROM AUTHOR]

It was previously reported that normobaric oxygen therapy (NBO) significantly affected T2 ∗ -weighted imaging in a mouse model of intracerebral hemorrhage (ICH). However, it is unclear whether a similar phenomenon exists in large volume ICH as seen in human pathology. We investigated the effects of NBO on T2 ∗ -weighted images in a pig model of ICH. Our data show that NBO makes disappear a peripheral crown of the hematoma, which in turn decreases the apparent volume of ICH by 18%. We hypothesized that this result could be translated to ICH in human, and subsequently could lead to inaccurate diagnostic. [ABSTRACT FROM AUTHOR]

• Current imaging techniques do not allow for the detection of vascular activation. • Immuno-MRI uses microparticles of iron oxide (MPIO) targeting adhesion molecules. • It emerges as a promising non-invasive tool to detect neuroinflammation during stroke. • It can assess disease severity, predict outcomes, and monitor treatment response. • Biodegradable MPIOs could facilitate clinical translation. Following a stroke, an inflammatory response occurs, characterized by an increased blood–brain barrier permeability, expression of endothelial trafficking molecules, and infiltration of immune cells. Adhesion molecules expressed on activated brain endothelial cells are potential biomarkers of intraparenchymal inflammation. However, in current clinical practice, it is not possible to measure endothelial activation using clinically available imaging. Using targeted micro-sized particles of iron oxide (MPIO), immuno-MRI enables the detection of endothelial adhesion molecules at high resolution and, consequently, facilitates the detection of stroke-induced brain inflammation. In this review, we highlight the most recent studies that used immuno-MRI in models of neurovascular disorders, including transient ischemic attack, ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage. We also discuss the potential of immuno-MRI in clinical practice and the necessary next steps for its implementation in patients. [ABSTRACT FROM AUTHOR]

Abstract: Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro-neurotoxic effect of endogenous tissue plasminogen activator (tPA) via N-methyl-d-Aspartate (NMDA) receptors. Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy (αATD-GluN1 antibody) preventing the interaction of tPA with NMDA receptors. We found that a single intravenous injection of αATD-GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume. [Copyright &y& Elsevier]

Intraventricular hemorrhage (IVH) is the most severe form of stroke with intraventricular fibrinolysis (IVF) as a hopeful treatment. Urokinase (uPA) and tissue-type plasminogen activator (tPA) are used for IVF in Human. No clinical trial has evaluated the differential impact of these two fibrinolytics for IVF. Thus, we decided here to compare the use of these two fibrinolytics in a pre-clinical study. IVH was induced in rats by injection of collagenase type VII within the brain parenchyma followed by an IVF. Rats were randomized to receive uPA, tPA or saline within the ventricle, and cerebrospinal fluid was aspirated. Hematoma and ventricular volumes, brain water contents, inflammation and neurological deficits were measured at day three post-treatments. We also performed in vitro studies, in which neuronal cultures were subjected to an excitotoxic paradigm in the presence of either uPA or tPA. In the IVH model, we showed that although both uPA and tPA led to reduced ventricular volumes, only uPA significantly improved functional recovery. These results could be explained by the fact that uPA, in contrast of tPA, fails to promote inflammatory processes and neurotoxicity. Our study provides evidence supporting the use of uPA for fibrinolysis of IVH. A clinical trial could be warranted if tPA failed to improve outcomes in human IVH. [ABSTRACT FROM AUTHOR]