Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier

Szmydynger‐Chodobska, Joanna; Strazielle, Nathalie; Gandy, Jessica R.; Keefe, Timothy H; Zink, Brian J.; Ghersi-Egea, Jean-François; Chodobski, Adam

doi:10.1038/jcbfm.2011.111

Cited by 113 publications

(91 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CCL2 is rapidly upregulated in response to a variety of acute and chronic CNS disorders [32], including neonatal brain injury in rodent models [33] and human infants [34]. CCL2 is released across the apical and basolateral membranes of the choroid epithelium and can mediate leukocyte recruitment to the choroid plexus [35,36]. Of note, functional inhibition of CCL2 by using a neutralizing antibody protects the neonatal rat brain from acute excitotoxic injury [37].…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Bi¹,

Qiao²,

Bergelson³

et al. 2015

J Infect Dis.

View full text Add to dashboard Cite

Background. Staphylococcus epidermidis causes late-onset sepsis in preterm infants. Staphylococcus epidermidis activates host responses in part via Toll-like receptor 2 (TLR2). Epidemiologic studies link bacteremia and neonatal brain injury, but direct evidence is lacking.Methods. Wild-type and TLR2-deficient (TLR2−/−) mice were injected intravenously with S. epidermidis at postnatal day 1 prior to measuring plasma and brain cytokine and chemokine levels, bacterial clearance, brain caspase-3 activation, white/gray matter volume, and innate transcriptome.Results. Staphylococcus epidermidis bacteremia spontaneously resolved over 24 hours without detectable bacteria in the cerebrospinal fluid (CSF). TLR2−/− mice demonstrated delayed S. epidermidis clearance from blood, spleen, and liver. Staphylococcus epidermidis increased the white blood cell count in the CSF, increased interleukin 6, interleukin 12p40, CCL2, and CXCL1 concentrations in plasma; increased the CCL2 concentration in the brain; and caused rapid (within 6 hours) TLR2-dependent brain activation of caspase-3 and TLR2-independent white matter injury.Conclusions. Staphylococcus epidermidis bacteremia, in the absence of bacterial entry into the CSF, impairs neonatal brain development. Staphylococcus epidermidis bacteremia induced both TLR2-dependent and -independent brain injury, with the latter occurring in the absence of TLR2, a condition associated with an increased bacterial burden. Our study indicates that the consequences of transient bacteremia in early life may be more severe than commonly appreciated, and our findings may inform novel approaches to reduce bacteremia-associated brain injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Bi¹,

Qiao²,

Bergelson³

et al. 2015

J Infect Dis.

View full text Add to dashboard Cite

show abstract

“…75 Like the endothelial cells of the BBB, the CPE cells express tight junctions and serve as a barrier to separate the CNS from the circulation, and the migration across the BCSFB is restricted. However, monocytes 76,77 and T cells 78 have been shown to enter the CNS via the BCSFB in response to injury. It is known that JCPyV entry 5-HT 2 receptors are expressed in the CPE 79,80 and that 5-HT 2C isolated from the rat choroid plexus is N-glycosylated.…”

Section: Direct Binding Of Jcpyv To Barriers Of the Cnsmentioning

confidence: 99%

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

Haley

O’Hara

Nelson

et al. 2015

The American Journal of Pathology

View full text Add to dashboard Cite

The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal a2,6elinked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. (Am J Pathol 2015, 185: 2246e2258; http://dx.doi.org/10.1016/j.ajpath.2015.04.003)The human polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rapidly progressing, often fatal neurodegenerative disease. Although PML is rare, JCPyV infection is widespread, infecting approximately 50% to 80% of the healthy adult population. 1,2 As the initial infection is asymptomatic, the mode of JCPyV transmission is unknown. The virus establishes a persistent infection in the kidney and urinary tract of immunocompetent hosts, 3 and about 20% of these infected individuals shed virus in their urine. 4 JCPyV DNA has also been detected in other tissues, including B lymphocytes in the bone marrow, tonsillar stromal cells, lungs, spleen, and brain, 5e13 suggesting additional sites of viral persistence. The route of viral transmission from the initial site(s) of infection and latency to the central nervous system (CNS), the main site of pathogenesis, is not clearly understood.Under conditions of immunosuppression, JCPyV infects and destroys the myelin-producing oligodendrocytes, resulting in demyelination, which is the hallmark of this fatal disease; to a Supported by NIH grants R01NS043097 (W.J.A.) and P01NS065719 (W.J.A.).

show abstract

“…The mechanisms of endothelial and epithelial transmigration, however, are not fully elucidated. Few studies were able to provide direct evidence for the migration of immune cells from the choroid plexus stroma across the BCSFB into the ventricle in vivo [154,155]. Especially studies in EAE have failed to provide direct in vivo evidence for the localization of T cells between choroid plexus epithelial cells providing proof of their passage across the epithelium [41,114].…”

Section: Neuroimmune Function Of the Choroid Plexuses In Neurologicalmentioning

confidence: 99%

“…The site of injury may, however, be relevant for the function of the choroid plexuses in promoting anti-inflammatory or inflammatory cues. In traumatic brain injury a rapid increase in synthesis and release of diverse CXCL chemokines and CCL2 from the choroid plexus epithelium has been observed [154,155] and was accompanied by the invasion of monocytes and neutrophils in between choroid plexus epithelial cells [154]. Pathogen-derived TLR ligands also induce an accumulation of innate immune cells in the CSF and choroid plexus in the developing brain [98].…”

Section: Neuroimmune Function Of the Choroid Plexuses In Neurologicalmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

Self Cite

View full text Add to dashboard Cite

The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

show abstract

Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier

Cited by 113 publications

References 36 publications

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Contact Info

Product

Resources

About