Choroid Plexus: A Key Player in Neuroprotection and Neuroregeneration
Conrad Johanson1, John Duncan1, Donald Palm1, Andrew Baird2,3 , Edward Stopa1 and Paul McMillan1
1 - Department of Clinical Neurosciences, Brown Medical School, Providence, RI 02903,
2 - Human BioMolecular Research Institute, San Diego, CA 92121
3 - Molecular Neuroscience Group, School of Medicine, University of Birmingham, Egbaston, UK
Received 22 December 2004; received in revised form 29 January 2005; accepted 1 February 2005
Correspondence and requests for reprints should be addressed to:
Prof Conrad E. Johanson
Rhode Island Hospital
593 Eddy Street
Providence, RI 02903 USA
Tel 401-444-8739
Fax 401-444-8727
Email: Conrad_Johanson@Brown.edu
Abstract
Due to the location of the choroid plexus (CP) tissues in the brain interior, and the unique gene expression properties of this epithelial interface with blood and CSF, there are many opportunities for regulating the transfer of growth factors and neurotrophins into the ventricles and adjacent brain regions. The choroidal secretion of a wide array of peptides and proteins impacts neuroprotective and regenerative functions of targeted cells in many networks throughout the CNS. The ability of CP to function as a ‘multipurpose organ’ and be involved in a plethora of homeostatic roles suggests heterogeneity and plasticity of its epithelium. Evidence is presented for subpopulations of CP epithelial cells. Using the lectin probe wheat germ agglutinin (WGA) which binds sialic acid, we show regional differences in the expression of sialic acid residues at the proximal, middle and distal regions of CP fronds. Such epithelial heterogeneity is consistent with the diverse functions subserved by CP. New information is also presented for the ability of the blood-CSF barrier in aged animals (18-mo-old rats) to rapidly repair itself after a severe 10-min stroke (transient forebrain ischemia) followed by reperfusion. CP growth factor systems, e.g., FGF2, which help to repair the disabled adult brain are evidently the same as those which drive CNS development. Therefore, we postulate that brain-CSF recovery recapitulates ontogeny. The efficient ability of CP to stabilize itself after ischemic injury suggests pharmacological opportunities for manipulating the transport of growth factors and neurotrophins into CSF to expedite neuroviability in aging and states of degeneration. We also discuss possible application of biotechnological techniques, i.e., transplants, encapsulation and viral vectors, to foster neuroprotection and regeneration by enhancing choroidal secretions into CSF.
Outline
I. Foundational Principles of CSF Homeostasis and Brain Fitness over the Lifespan
Generative Development
Healthy Adulthood
Degenerative Aging
II. Working Hypothesis: CSF-Brain Recovery Recapitulates Ontogeny
III. Subpopulations of Choroid Plexus (CP) Epithelial Cells and CSF Functions
IV. The Role of Transport at the Blood-CSF Interface in Neuroprotection
Trauma
Cerebral Ischemia and Subarachnoid Hemorrhage
Alzheimer’s Disease and Age-related Dementias
V. Surgical, Mechanical and Pharmacological Approaches to Modify
the Choroid Plexus-CSF System: Implications for Neuroregeneration
Transplanted Epithelium
Cultured Choroidal Cells
Encapsulated Choroid Plexus
An Artificial Choroid Plexus Pump?
Choroidally-Directed Viral Vectors
VI. Enhancing CP-CSF Functions to Expedite Neuroprotection and Regeneration
VII. An Evolving CSF Research Paradigm for Promoting Neuroviability
VIII. Concluding Remarks
References
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