Failure of multiple sclerosis (MS) lesions to resolve in the months after they form leads to smouldering demyelination and axon degeneration, identifiable in vivo as paramagnetic rim lesions on MRI. [1][2][3] To define mechanisms underlying this disabling, progressive neurodegenerative state, 4-6 and to foster development of new therapeutics, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter (WM)

Intracranial haemorrhages, including intracerebral haemorrhage (ICH), intraventricular haemorrhage (IVH) and subarachnoid haemorrhage (SAH), are leading causes of morbidity and mortality worldwide. In addition, haemorrhage contributes to tissue damage in traumatic brain injury (TBI). To date, efforts to treat the long-term consequences of cerebral haemorrhage have been unsatisfactory. Incident rates and mortality have not showed significant improvement in recent years. In terms of secondary damage following haemorrhage, it is becoming increasingly apparent that blood components are of integral importance, with haemoglobin-derived iron playing a major role. However, the damage caused by iron is complex and varied, and therefore, increased investigation into the mechanisms by which iron causes brain injury is required. As ICH, IVH, SAH and TBI are related, this review will discuss the role of iron in each, so that similarities in injury pathologies can be more easily identified. It summarises important components of normal brain iron homeostasis and analyses the existing evidence on iron-related brain injury mechanisms. It further discusses treatment options of particular promise.

Background Neonatal germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH) is common and often results in hydrocephalus. The pathogenesis of post-hemorrhagic hydrocephalus is not fully understood. Objective To explore the potential role of hemoglobin and iron released after hemorrhage. Methods Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated. Results Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared to injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared to aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death. Conclusion Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for pathogenesis and treatment of post-hemorrhagic hydrocephalus.

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