Parallel Development of Choroid Plexus Degeneration and Meningeal Inflammation in Subarachnoid Hemorrhage – Experimental Study

Abstract

Background. The choroid plexuses (CPs) are brain structures located in the brain ventricles, involved in the production and reabsorption of cerebrospinal fluid (CSF) components, cerebral immune surveillance, and various endocrine-enzymatic activities and acts as a CSF-blood barrier. This study investigated to determine if there is a link between ischemic CP injury and meningo-cerebral inflammation processes. Material and Methods. This study was conducted on 18 rabbits. Four rabbits were used as the baseline group to examine the normal structures. Fourteen of the rabbits were used as the study group by injecting 1.00cc of homologous blood into their cisterna magna. The animals were followed by daily monitoring for ten days and then slaughtered. Apoptotic degeneration of the CP cells was determined and statistical analyses were carried out using normal and apoptotic CP cell numbers. Data analyses were comprised of Mann-Whitney U tests. Differences were considered to be significant if p < 0.005. Results. Five animals belonging to the study group died between the 5 th and 8 th days. Unconsciousness, neck stiffness, convulsion, fever, apnea, cardiac arrhythmia, and breathing disturbances were observed in all of the animals who subsequently died. Intraventricular blood leakage was detected in all the dead and three surviving animals. Choroidal artery spasm, choroidal ependymal cell injury, choroidal cell apoptosis, pia-arachnoid thickening, meningocortical adhesions and blood cell density in the subarachnoid spaces were more severe in the more CP degenerated animals than those of the others. There were significant differences between the apoptotic CP cell density and blood cell density in the subarachnoid spaces (p < 0.005). Conclusions. Subarachnoid hemorrhage (SAH) extending to brain ventricles causes ischemic degeneration of the CP by way of triggered choroidal artery vasospasm. It should be emphasized that the prevention of CP function may be an important part of the protection of the brain in SAH (Adv Clin Exp Med 2014, 23, 5, 699-704).

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

“…↓ CSF secretion [198] ↑ mRNA for NF-κB, MCP-1, IL1R1, IL-8, IL-6, FAS, TNF-α expression [183] ↑ Iba-1+ and CD68+ epiplexus cells [186] ↑ Number of cytoplasmic water vesicles [191][192][193] ↑ HO-1 expression [183] ↑ AQP1 expression [194] Activation of TLR4 [182] Ischemic Apoptosis or necrosis according to the severity of ischemic injury [201] ↑ ED1+ number, CR3 receptors, expression of MHC I and MHC II antigens [217] ↑ Calcium transfer to CSF [210] Alteration in B-CSF barrier after middle cerebral artery occlusion [207] ↑ Apoptotic cells characterized by nuclear DNA fragmentation after middle cerebral artery occlusion [201] ↑ iNOS expression in epiplexus cells, Number of OX-42+ , ED1+ , OX-18+ , OX-6+ cells in epiplexus position [217] ↑ Permeability of B-CSF barrier for inulin after bilateral carotid occlusion [205] ↑ Expression of TGFβ1, brain-derived neurotrophic factor and other growth factors [216] ↑ MMP-9 expression in infiltrating macrophages [214] ↑ VEGF and eNOS expression [217,218] Plasma membrane and organelle damage; clumping of nuclear chromatin after forebrain ischemia [205,206] ↑ Number of macrophages [220] ↑ CP epithelial cell proliferation Expression of NeuN and GFAP after middle cerebral artery occlusion [215] CP as invasion route for T cells into the ischemic brain [219] Edema, apoptosis of CP epithelial cells after middle cerebral artery occlusion Indistinct epithelial membranes and varying degrees of pyknosis after middle cerebral artery occlusion [214] Desquamation of CP epithelial cells [199] ↓ AQP1 expression up to 24 h ↑ AQP1expression between 24-48 h after global cerebral ischemia [209] ↑ VCAM-1, MAdCAM-1, C3CL1, Nt5e expression [220] Traumatic TBI ↑ Intercellular spaces between CP epithelial cells [225] ↑ Macrophage number in epiplexus position after non-penetrative injury…”

“…Vasospasm of the CP arteries was induced 20 days after SAH followed by ischemic injury, apoptosis of CP cells and decreased secretion of CSF [198]. It seems that degeneration of CP cells increases in severity depending on the volume of blood in the subarachnoid space [199]. Nevertheless, hydrocephalus may also occur in the absence of CSF hypersecretion probably due to desquamation of the ependymal and CP epithelial cells leading to reduction of cerebral aqueduct volume [200].…”

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

“…There was a marked increase in the numbers of such spaces, particularly at 2 days and the authors hypothesized that these changes may be related to altered CSF secretion. Furthermore, changes in CP morphology, with reduced epithelial cell and microvillus height, and many TUNEL-positive cells have been reported 10 days after SAH (24% of cells in animals surviving SAH and 42% in animals that died) [47]. …”

Médula espinal quemada en el líquido cefalorraquídeo ácido durante la hemorragia subaracnoidea: estudio experimental

“…Hence, there may be a significant link between choroid plexus and cerebrospinal fluid pH regulation. SAH may extend to brain ventricles and causes ischemic degeneration of the choroid plexus by way of triggered choroidal artery vasospasm 9 .…”