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Transforming Growth Factor-β and CNS Scarring
Published in Martin Berry, Ann Logan, CNS Injuries: Cellular Responses and Pharmacological Strategies, 2019
Between the astrocytic processes and the mesenchymal core a basal lamina is deposited, probably by the astrocytes under the influence of fibroblasts, and a limiting membrane (glia limitans) starts to organise which eventually delineates the cut edges of neuropil. The glia limitans established in the wound is identical to, and continuous with, that of the external limiting glial membrane. A dense fibrous scar which is surrounded by a glial membrane is thereby constructed within the wound between 5 and 8 days. During this period an angiogenic response also occurs in the neuropil bordering the wound. By 8 to 14 days, the trilaminar scar is fully formed, the central mesenchymal fibrous core contracted, and the palisades of astrocyte processes compacted at the lesion margins (see Chapter 1). GFAP-activity in astrocytes thereafter declines, except at the wound margins, and a small number of macrophages remain in the core, but none are seen in the surrounding CNS tissue. By 14 days, all newly grown axonal processes have died back to their original parent axons, a large number of which remain in situ in perpetuity, making no further attempt to grow. This abortion of regeneration coincides with the maturation of the impenetrable fibrous glial scar and functional reconnection of severed neural pathways is therefore impossible.
Neuroviral Infections and Immunity
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
Bersabeh Tigabu, Fabian de Kok-Mercado, Michael R. Holbrook
The BBB is a critical component of the CNS in that it limits the flow of material between the general circulation, either lymphatic or circulatory, and the CNS. The principal components of the BBB include brain microvascular endothelial cells (BMVECs), the basement membrane (BM), which includes the glial cells, neurons, and perivascular pericytes, which together form a neurovascular unit (Cardoso et al. 2010; Persidsky et al. 2006 b) (Figure 2.1). The endothelial cell BM is composed of structural and specialized proteins that include collagen, elastin, fibronectin, lam-Min, and proteoglycans along with adhesion molecules. The glia limitans, which is the parenchymal basal membrane composed of astrocyte processes, provides an additional physical barrier to lymphocyte migration (Roberts et al. 2010). The glia limitans covers the external face of the brain and spinal cord and also surrounds blood vessels. Astrocytes extend their feet to abut the abluminal face of the endothelial cells and both the astrocytes and endothelial cells are innervated by neurons to provide an additional means of regulating BBB activity (Roberts et al. 2010). The physical architecture of the BBB is not consistent between components of the vascular system. Importantly, the specific architecture of the BBB varies dependent upon the type of blood vessel and its location relative to the CNS (Engelhardt 2008; Owens et al. 2008). Capillaries have little space between endothelial cells and the glia limi-tans, while arteries and veins incorporate additional components such as smooth muscle cells. Postcapillary venules contain a perivascular space containing “mural cells” (Owens et al. 2008). The perivascular space is also the home for a number of antigen-presenting cells (APCs) including macrophages and mesothelial cells and is also a significant point of regulation for transit of cells and materials across the BBB (Owens et al. 2008).
Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations
Published in Fetal and Pediatric Pathology, 2023
Silvia Zago, Evelina Silvestri, Tiziana Arcangeli, Marina Calisesi, Chiara Romeo, Giulia Parmeggiani, Elena Parrini, Valentina Cetica, Renzo Guerrini, Andrea Palicelli, Maria Paola Bonasoni
Genetic analysis was prompted by brain histopathology, which showed cobblestone lissencephaly, with ectopic neuroglial tissue into the arachnoid space resulting in an extracortical neuroglial layer giving the cerebral surface an irregular appearance. Hypoglycosylation of the dystroglycans leads to barrier impairment of the glia limitans and subsequent breach resulting in abnormal cortical overmigration. The cortical agyria with the extracortical layer of neuroglial cells reduces or obliterates the pericerebral space, interfering with cerebrospinal fluid resorption, contributing to ventricular dilatation [14].
Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2020
Joost Smolders, Nina L. Fransen, Cheng-Chih Hsiao, Jörg Hamann, Inge Huitinga
The PVS is the only compartment in the human body, which is bordered by two basal membranes, an endothelial and a parenchymal basement membrane (EBM and PBM), respectively[57]. These basement membranes are made of extracellular matrix molecules, including laminin, fibronectin, and collagen type IV[58]. On the luminal side, specialized endothelium with tight junction covers the EBM to form the BBB. On the parenchymal side, astrocyte end-feet form the glia limitans, covering the PBM. The glia limitans forms with astrocytic tight junctions a secluded barrier between the PVS and the parenchyma[59]. The PVS plays a crucial role in the drainage of the suggested CNS flow of interstitial fluid[60], which removes waste products from the parenchyma. Therefore, the PVS could be an excellent hub to screen for antigens. The PVS is populated by a variety of APCs, including specialized perivascular macrophages[61]. Although disputed, the presence of perivascular macrophages has been reported in the PVS of white matter venules[62]. The compartmentalization of TRM cells in the PVS could be mediated by their signature surface markers. CD69 interferes with sphingosine 1-phospate receptor 1 (S1P1) to prevent tissue egress, CD49a is a receptor for collagen type IV, and the TRM-associated molecule CD44 is a receptor for laminin[63]. Finally, a ligand for CD103 is E-cadherin, which has been described on activated CD103+ lymphocytes, enabling cluster formation [57,63]. Interaction of these receptors with their ligands may mediate the homing and clustering of brain TRM cells in the PVS. We assume them being under tight control by surrounding signals in the PVS, while awaiting potential reactivation. An interesting candidate for providing this local control of reactivation is the perivascular macrophage. The perivascular macrophage can present antigens yet can also express the inhibitory cytotoxic T lymphocyte-associated protein 4 (CTLA-4) ligand CD86, which may prevent activation of brain TRM cells[64]. Moreover, activated astrocytes may present the inhibitory programmed death-1 (PD-1) ligand PD-L1 to the TRM cells via their end-feet at the glia limitans[42].
Brain microvascular pathology in Susac syndrome: an electron microscopic study of five cases
Published in Ultrastructural Pathology, 2019
Dimitri P. Agamanolis, Richard A. Prayson, Negar Asdaghi, Sakir H. Gultekin, Kim Bigley, Robert M. Rennebohm
The blood vessels that were present in the samples ranged approximately from 5 to 10 microns in diameter and did not have smooth muscle cells in their walls, most consistent with capillaries and venules. The findings were similar in the five cases and will be described together. The most prevalent change, present in all cases, involved the vascular wall and basement membrane (BM). Cerebral blood vessels have two BM components: the endothelial BM and the astrocytic (glia limitans perivascularis) BM, which is continuous with glia limitans superficialis that covers the surface of the brain. Proximal to capillaries, there is a space (perivascular or Virchow-Robin space) between vessels and the glia limitans BM. This space, which may contain a small amount of collagen, narrows progressively and disappears at the level of capillaries, at which point the two BMs are fused and are separated only in areas where perithelial cells (pericytes-PC) are found.16-18 However, some capillaries may still have a narrow perivascular space.18 In SuS, the two components of the BM were widely separated and the outer (astrocytic) BM was frequently irregularly folded. The space between them (the perivascular space) was filled with a large amount of collagen and granular material and contained also cell debris and rare lymphocytes (Figures 1–4). In one case (Patient 1), this space contained crystal-like deposits suggestive of calcification (Figure 5(a)), and the vessel wall was thickened due to deposition of layers of banded collagen (Figure 5(b)). Some vessels showed a diffuse thickening of BMs (Figure 6(a)). Some vessels showing these changes had patent lumina with variable and some with severe narrowing (Figures 1 and 4). In other vessels, the lumen was collapsed (Figure 6(a)). Some vessels showed end stage changes, in which all normal cellular components were lost, leaving behind a ghost structure consisting of BM mixed with collagen and cell processes (Figure 6(b,c)). The perivascular spaces contained also vacuolated (lipid laden) macrophages (Figure 6(d)), rare lymphocytes and other mononuclear cells (Figures 2 and 6(d)), and reactive astrocytes, some of which had diverse lysosomal products. Small perivascular extravasations of RBCs (microbleeds) were present in three cases. There was loss of myelinated axons resulting in empty microcystic areas around abnormal vessels. Endothelial swelling leading to collapse of the capillary lumen, which could be construed as early changes, were seen infrequently. No tubuloreticular inclusions were seen in any case.