Challenges for intraventricular hemorrhage research and emerging therapeutic targets

Abstract

Introduction – Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy that improves neurological outcome in either population highlighting the need for additional focus on therapeutic targets and treatments emerging from preclinical studies. Areas Covered – IVH induces both initial injury linked to the physical effects of the blood (mass effect) and secondary injury linked to the brain response to the hemorrhage. Preclinical studies have identified multiple secondary injury mechanisms following IVH, and particularly the role of blood components (e.g. hemoglobin, iron, thrombin). This review, with an emphasis on pre-clinical IVH research, highlights therapeutic targets and treatments that may be of use in prevention, acute care, or repair of damage. Expert Opinion – An IVH is a potentially devastating event. Progress has been made in elucidating injury mechanisms, but this has still to translate to the clinic. Some pathways involved in injury also have beneficial effects (coagulation cascade/inflammation). A greater understanding of the downstream pathways involved in those pathways may allow therapeutic development. Iron chelation (deferoxamine) is in clinical trial for intracerebral hemorrhage and preclinical data suggest it may be a potential treatment for IVH.

Brain endothelial cell junctions after cerebral hemorrhage: Changes, mechanisms and therapeutic targets

“…[39][40][41] It should be noted, however, that the main effect of intraventricular blood in relation to brain water is post-hemorrhagic hydrocephalus. That is related to altered CSF dynamics (blockage in CSF drainage and/or increased CSF secretion 42,43 )…”

Prediction of cerebral hemorrhagic supratentorial stroke acute period outcome on the basis of the assessment of secondary intraventricular hemorrhage severity in the onset of the disease

“…30-45 % of cases of spontaneous intracerebral hemorrhage (SICH) are complicated by intraventricular hemorrhage (IVH) [5,6]. In accordance with the numerous studies, the presence of secondary IVH is an independent predictor of early clinical deterioration and poor outcome in patients with SICH [4,9,10], which suggests the presence of secondary IVH in the spectrum of parameters associated with the acute period outcome of the disease [11].…”

Effects of Thyroid Hormones on Risk of Intraventricular Hemorrhage in Preterm Infants

“…IVH in preterm infants usually originates from the germinal matrix and is almost common in infants who are prematurely born or have low birth weight [13]. In premature infants, the more common cause of IVH is the change in the permeability of the subtle structures of the cell in the developing brain.…”