Central Nervous System Fibroblast-Like Cells in Stroke and Other Neurological Disorders

Xu, Lingling; Yao, Yao

doi:10.1161/strokeaha.120.033431

Cited by 20 publications

(14 citation statements)

References 85 publications

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“…Classical spinal cord glial scars also contain fibroblasts that originate from meninges, choroid plexus, and perivascular spaces ( Dorrier et al, 2021 ; Silver and Miller, 2004 ; Xu and Yao, 2021 ). In the rat DFP study, no trauma was involved.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy

Gage

Gard

Thippeswamy

2022

Front. Cell Dev. Biol.

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Glial scars have been observed following stab lesions in the spinal cord and brain but not observed and characterized in chemoconvulsant-induced epilepsy models. Epilepsy is a disorder characterized by spontaneous recurrent seizures and can be modeled in rodents. Diisopropylfluorophosphate (DFP) exposure, like other real-world organophosphate nerve agents (OPNAs) used in chemical warfare scenarios, can lead to the development of status epilepticus (SE). We have previously demonstrated that DFP-induced SE promotes epileptogenesis which is characterized by the development of spontaneous recurrent seizures (SRS), gliosis, and neurodegeneration. In this study, we report classical glial scars developed in the piriform cortex, but not in the hippocampus, by 8 days post-exposure. We challenged both male and female rats with 4–5 mg/kg DFP (s.c.) followed immediately by 2 mg/kg atropine sulfate (i.m.) and 25 mg/kg pralidoxime (i.m.) and one hour later by midazolam (i.m). Glial scars were present in the piriform cortex/amygdala region in 73% of the DFP treated animals. No scars were found in controls. Scars were characterized by a massive clustering of reactive microglia surrounded by hypertrophic reactive astrocytes. The core of the scars was filled with a significant increase of IBA1 and CD68 positive cells and a significant reduction in NeuN positive cells compared to the periphery of the scars. There was a significantly higher density of reactive GFAP, complement 3 (C3), and inducible nitric oxide synthase (iNOS) positive cells at the periphery of the scar compared to similar areas in controls. We found a significant increase in chondroitin sulfate proteoglycans (CS-56) in the periphery of the scars compared to a similar region in control brains. However, there was no change in TGF-β1 or TGF-β2 positive cells in or around the scars in DFP-exposed animals compared to controls. In contrast to stab-induced scars, we did not find fibroblasts (Thy1.1) in the scar core or periphery. There were sex differences with respect to the density of iNOS, CD68, NeuN, GFAP, C3 and CS-56 positive cells. This is the first report of cortical glial scars in rodents with systemic chemoconvulsant-induced SE. Further investigation could help to elucidate the mechanisms of scar development and mitigation strategies.

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Section: Discussionmentioning

confidence: 99%

Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy

Gage

Gard

Thippeswamy

2022

Front. Cell Dev. Biol.

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“…CNS fibroblasts include meningeal fibroblasts and perivascular fibroblasts, which are located in all three layers of the meninges (pia, arachnoid, and dura) and perivascular space, respectively. 136,137 Under physiological conditions, perivascular fibroblasts are sandwiched between vSMCs and astrocytic endfeet in large blood vessels. 38,136 Our unpublished data showed that fibroblasts were associated with small blood vessels after hemorrhagic stroke, suggesting a possible role of fibroblasts in BBB regulation under pathological conditions.…”

Section: Expression and Functions Of Laminin And Its Receptors In The...mentioning

confidence: 99%

“…136,137 Under physiological conditions, perivascular fibroblasts are sandwiched between vSMCs and astrocytic endfeet in large blood vessels. 38,136 Our unpublished data showed that fibroblasts were associated with small blood vessels after hemorrhagic stroke, suggesting a possible role of fibroblasts in BBB regulation under pathological conditions.…”

Section: Expression and Functions Of Laminin And Its Receptors In The...mentioning

confidence: 99%

Cell-specific expression and function of laminin at the neurovascular unit

Nirwane

Yao

2022

J Cereb Blood Flow Metab

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Laminin, a major component of the basal lamina (BL), is a heterotrimeric protein with many isoforms. In the CNS, laminin is expressed by almost all cell types, yet different cells synthesize distinct laminin isoforms. By binding to its receptors, laminin exerts a wide variety of important functions. However, due to the reciprocal and cell-specific expression of laminin in different cells at the neurovascular unit, its functions in blood-brain barrier (BBB) maintenance and BBB repair after injury are not fully understood. In this review, we focus on the expression and functions of laminin and its receptors in the neurovascular unit under both physiological and pathological conditions. We first briefly introduce the structures of laminin and its receptors. Next, the expression and functions of laminin and its receptors in the CNS are summarized in a cell-specific manner. Finally, we identify the knowledge gap in the field and discuss key questions that need to be answered in the future. Our goal is to provide a comprehensive overview on cell-specific expression of laminin and its receptors in the CNS and their functions on BBB integrity.

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“…Fibroblast-like cells are common in the connective tissue of peripheral organs (Xu and Yao 2021 ). Within the CNS their location is mostly restricted to the basal laminae of the vascular system (Soderblom et al 2013 ).…”

Section: The Pathobiology Of the Glial Scarmentioning

confidence: 99%

The role of neural stem cells in regulating glial scar formation and repair

et al. 2021

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Glial scars are a common pathological occurrence in a variety of central nervous system (CNS) diseases and injuries. They are caused after severe damage and consist of reactive glia that form a barrier around the damaged tissue that leads to a non-permissive microenvironment which prevents proper endogenous regeneration. While there are a number of therapies that are able to address some components of disease, there are none that provide regenerative properties. Within the past decade, neural stem cells (NSCs) have been heavily studied due to their potent anti-inflammatory and reparative capabilities in disease and injury. Exogenously applied NSCs have been found to aid in glial scar healing by reducing inflammation and providing cell replacement. However, endogenous NSCs have also been found to contribute to the reactive environment by different means. Further understanding how NSCs can be leveraged to aid in the resolution of the glial scar is imperative in the use of these cells as regenerative therapies. To do so, humanised 3D model systems have been developed to study the development and maintenance of the glial scar. Herein, we explore the current work on endogenous and exogenous NSCs in the glial scar as well as the novel 3D stem cell–based technologies being used to model this pathology in a dish.

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Central Nervous System Fibroblast-Like Cells in Stroke and Other Neurological Disorders

Cited by 20 publications

References 85 publications

Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy

Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy

Cell-specific expression and function of laminin at the neurovascular unit

The role of neural stem cells in regulating glial scar formation and repair

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