Choroid plexus as a barrier to immunoglobulin delivery into cerebrospinal fluid

Aleshire, Stephen L.; Hajdu, I; Bradley, Charles; Parl, Fritz F.

doi:10.3171/jns.1985.63.4.0593

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…Another study provided evidence that IgG undergoes unidirectional apical to basolateral (ventricular efflux) transport by cultured CPECs [ 35 ]. These results were consistent with negligible IgG CSF entry across the CPs [ 200 ]. However, it is still uncertain to what extent and by which cellular mechanisms CPECs efflux proteins.…”

Section: Targeting the Choroid Plexuses For Brain Delivery: Futilesupporting

confidence: 83%

Targeting the Choroid Plexuses for Protein Drug Delivery

et al. 2020

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Delivery of therapeutic agents to the central nervous system is challenged by the barriers in place to regulate brain homeostasis. This is especially true for protein therapeutics. Targeting the barrier formed by the choroid plexuses at the interfaces of the systemic circulation and ventricular system may be a surrogate brain delivery strategy to circumvent the blood-brain barrier. Heterogenous cell populations located at the choroid plexuses provide diverse functions in regulating the exchange of material within the ventricular space. Receptor-mediated transcytosis may be a promising mechanism to deliver protein therapeutics across the tight junctions formed by choroid plexus epithelial cells. However, cerebrospinal fluid flow and other barriers formed by ependymal cells and perivascular spaces should also be considered for evaluation of protein therapeutic disposition. Various preclinical methods have been applied to delineate protein transport across the choroid plexuses, including imaging strategies, ventriculocisternal perfusions, and primary choroid plexus epithelial cell models. When used in combination with simultaneous measures of cerebrospinal fluid dynamics, they can yield important insight into pharmacokinetic properties within the brain. This review aims to provide an overview of the choroid plexuses and ventricular system to address their function as a barrier to pharmaceutical interventions and relevance for central nervous system drug delivery of protein therapeutics. Protein therapeutics targeting the ventricular system may provide new approaches in treating central nervous system diseases.

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Section: Targeting the Choroid Plexuses For Brain Delivery: Futilesupporting

confidence: 83%

Targeting the Choroid Plexuses for Protein Drug Delivery

et al. 2020

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“…Similarly, tight junctions linking epithelial cells of the choroid plexus serve as the blood–CSF barrier. Although these two barriers are reportedly impermeable to IgG under normal conditions (Aleshire et al, 1985; Seitz et al, 1985), Aihara et al (1994) have suggested that these barriers are not absolute to IgG. At least three schemes may explain unusual permeability of the barriers to IgG.…”

Section: Discussionmentioning

confidence: 99%

Mouse brain IgG‐like immunoreactivity: Strain‐specific occurrence in microglia and biochemical identification of IgG

Hazama¹,

Yasuhara²,

Morita³

et al. 2005

J of Comparative Neurology

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Unlike the brains of most mammals, the mouse brain appears unique in the massive appearance of cells showing IgG-like immunoreactivity, which has repeatedly been shown via immunohistochemistry. In the present study, we first examined possible species differences in IgG-like immunohistochemical staining in the brains of various rodents, including mice. In four of six mouse strains examined (ICR, Balb/c, C57BL/6, and AKR/J), antibodies against mouse IgG revealed positive staining in many brain microglia. However, no such positive staining was detected in brains of the rat, hamster, guinea pig, or two other mouse strains (CBA/N and CBA/J). We purified IgG-like-immunoreactive molecule(s) biochemically from brain of the ICR mouse as a representative mouse strain. Our amino-acid-sequence analysis proved that the purified protein was identical to serum IgG. The possibility of IgG synthesis by brain microglia in the ICR mouse was denied by our RT-PCR experiments and in situ hybridization histochemistry. In addition, Fcgamma-receptor-deficient double-knockout mice of the C57BL/6 genetic background contained no IgG-immunoreactive microglia in the brain. These results clearly indicate that microglial IgG staining is due to the uptake of serum IgG through Fcgamma receptors. However, the strain-specific mechanisms resulting in microglial IgG uptake remain to be elucidated, in that Fcgamma receptors are omnipresent in microglia of all rodents examined here.

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“…18 However, its broader function is the establishment and maintenance of baseline levels of the extracellular milieu throughout the brain and spinal cord, in part by secreting a wide range of growth factors into the CSF. Studies have confirmed the presence of numerous potent trophic factors within CP, including transforming growth factor-␤, GDF-15, GDNF, IGF2, NGF, NT-3, NT-4, BDNF, VEGF, and FGF2.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have confirmed the presence of numerous potent trophic factors within CP, including transforming growth factor-␤, GDF-15, GDNF, IGF2, NGF, NT-3, NT-4, BDNF, VEGF, and FGF2. 8,18,19 Currently, treatments for stroke are limited and the most effective pharmacotherapy (ie, systemic delivery of tissue plasminogen activator) produces limited therapeutic benefit, even when administered within 3 hours after stroke. 20 Central delivery of neurotrophic factors may represent an alternative means of enabling neuroprotection after stroke.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke

Borlongan¹,

Skinner²,

Geaney³

et al. 2004

Stroke

121

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Background and Purpose-Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies. Methods-In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP. For in vivo studies, rats received a 1-hour middle cerebral artery occlusion followed by intracranial transplantation of encapsulated or unencapsulated CP, empty capsules, or no transplant. Behavioral testing was conducted on days 1 to 3 after transplantation. Cerebral infarction was analyzed using 2,3,5-triphenyl-tetrazolium chloride staining at 3 days after transplantation. Results-Conditioned media from CP produced a significant dose-dependent protection of serum-deprived cortical neurons. Enzyme-linked immunosorbent assay confirmed secretion of GDNF, BDNF, and NGF from CP. Parallel in vivo studies showed that CP transplants improved behavioral performance and decreased the volume of infarction. Both encapsulated and unencapsulated CP transplants were effective; however, more robust benefits accompanied encapsulated transplants. Conclusions-These data are the first to demonstrate the neuroprotective potential of transplanted CP and raise the intriguing possibility of using these cells as part of the treatment regimen for stroke and other neurological disorders.

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Choroid plexus as a barrier to immunoglobulin delivery into cerebrospinal fluid

Cited by 7 publications

References 17 publications

Targeting the Choroid Plexuses for Protein Drug Delivery

Targeting the Choroid Plexuses for Protein Drug Delivery

Mouse brain IgG‐like immunoreactivity: Strain‐specific occurrence in microglia and biochemical identification of IgG

Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke

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