Inflammation of the Choroid Plexus and Ependymal Layer of the Ventricle Following Intraventricular Hemorrhage

Abstract

Intraventricular hemorrhage (IVH), which afflicts thousands of people of all ages every year, frequently results in the development of communicating hydrocephalus. Classically, IVH-induced hydrocephalus has been attributed to reduced resorption of cerebrospinal fluid (CSF) due to dysfunction of arachnoid granulations, but this explanation may be incomplete. We hypothesized that IVH would cause inflammation of the choroid plexus and of the ependymal lining of the ventricles, resulting in dysfunction of these barrier cells. Barrier dysfunction, in turn, would be expected to cause an increase in production of abnormal protein-rich CSF and transependymal migration of CSF. We tested this hypothesis using a rat model of IVH, in which 160 μl of autologous blood was infused into the lateral ventricle, resulting in a twofold increase in ventricular size 48 h later. In this model, we found significant activation of nuclear factor κB (NF-κB) signaling by the CSF barrier cells of the choroid plexus and ependymal lining. Moreover, these inflammatory changes were associated with abnormal uptake of serum-derived IgG by the barrier cells, a phenomenon closely linked to abnormal permeability of the blood–brain barrier. We conclude that inflammation marked by NF-κB signaling is a prominent feature after IVH and may account for certain pathophysiological sequelae associated with IVH.

Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy

“…Furthermore, the research studying the role of thrombin in post-hemorrhagic hydrocephalus has showed the grave BBB damage was resulted by intraventricular injection of thrombin, which was accompanied with impaired cilia of ependymal cells and swelling mitochondria near the lateral wall of ventricle [13]. Simard PF et al reported that remarked activation of nuclear factor B (NF-B) signaling by the choroid plexus and ependymal lining linked to increased BBB permeability in the animal model of IVH-induced hydrocephalus [21]. Another study on rats with communicating hydrocephalus showed the expression of GFAP and Iba-1 in the peri-ventricular and hippocampus area were correlated with severity of ventricular dilatation, indicating excessive reactive gliosis and neuroinflammation involved in the development of hydrocephalus [27].…”

Risk of Shunting After Aneurysmal Subarachnoid Hemorrhage

“…4,7,17,23 Studies have proposed several mechanisms on how inflammation predisposes to delayed hydrocephalus. It has been suggested that meningeal infection causes CSF flow disturbances, 4,17 ependymal cell dysfunction, and CSF barrier cell inflammation that lead to increased secretion of CSF 32 resulting in chronic hydrocephalus. It has been described that meningitis is associated with the duration of EVD, 33 as CSF sampling from EVD can increase the risk of meningitis.…”

Nuclear Factor κB Activation Impairs Ependymal Ciliogenesis and Links Neuroinflammation to Hydrocephalus Formation

“…In such inflammatory conditions, the IKK/NF-B system is activated (e.g., via TNF␣, IL-1, and TLR signaling) (Hayden and Ghosh, 2008). Interestingly, a recent study shows nuclear translocation of RelA in ependymal cells in a mouse model of intraventricular hemorrhages under conditions that induce hydrocephalus (Simard et al, 2011).…”