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      Brain iron overload following intracranial haemorrhage

      review-article
      , , ,
      Stroke and Vascular Neurology
      BMJ Publishing Group
      Brain, Hemorrhage, Subarachnoid

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          Abstract

          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.

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          Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.

          Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
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            Intraventricular hemorrhage in premature infants: mechanism of disease.

            Intraventricular hemorrhage (IVH) is a major complication of prematurity. IVH typically initiates in the germinal matrix, which is a richly vascularized collection of neuronal-glial precursor cells in the developing brain. The etiology of IVH is multifactorial and is primarily attributed to the intrinsic fragility of the germinal matrix vasculature and the disturbance in the cerebral blood flow (CBF). Although this review broadly describes the pathogenesis of IVH, the main focus is on the recent development in molecular mechanisms that elucidates the fragility of the germinal matrix vasculature. The microvasculature of the germinal matrix is frail because of an abundance of angiogenic blood vessels that exhibit paucity of pericytes, immaturity of basal lamina, and deficiency of glial fibrillary acidic protein (GFAP) in the ensheathing astrocytes endfeet. High VEGF and angiopoietin-2 levels activate a rapid angiogenesis in the germinal matrix. The elevation of these growth factors may be ascribed to a relative hypoxia of the germinal matrix perhaps resulting from high metabolic activity and oxygen consumption of the neural progenitor cells. Hence, the rapid stabilization of the angiogenic vessels and the restoration of normal CBF on the first day of life are potential strategies to prevent IVH in premature infants.
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              Serum ferritin: Past, present and future.

              Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. Copyright 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Stroke Vasc Neurol
                Stroke Vasc Neurol
                svn
                svn
                Stroke and Vascular Neurology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-8696
                December 2016
                19 December 2016
                : 1
                : 4
                : 172-184
                Affiliations
                Department of Neurosurgery, University of Michigan , Ann Arbor, Michigan, USA
                Author notes
                [Correspondence to ] Dr Guohua Xi; guohuaxi@ 123456umich.edu
                Article
                svn-2016-000042
                10.1136/svn-2016-000042
                5435218
                28959481
                e92bb9bb-16d0-46ab-9699-a1ab7d0ef847
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 19 September 2016
                : 1 November 2016
                : 2 November 2016
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke, http://dx.doi.org/10.13039/100000065;
                Award ID: NS-090925
                Categories
                1506
                Review

                brain,hemorrhage,subarachnoid
                brain, hemorrhage, subarachnoid

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