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Submitted on January 25, 2004
From the Neurology/Institute of Molecular Medicine and Genetics/School of Graduate Studies (C.V.B.), Medical College of Georgia, Augusta, Ga; the Research and Affiliations Service Line (C.V.B.), Augusta Veterans Affairs Medical Center, Augusta, Ga; LCT BioPharma, Inc (A.V.V, D.F.E.), Providence, RI; and Diatranz NZ Ltd/Living Cell Technologies (S.J.M.S., M.G., R.B.E.), Auckland, New Zealand. * To whom correspondence should be addressed. E-mail: cborlongan{at}mail.mcg.edu.
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.
Revised on May 18, 2004
Accepted on June 9, 2004
Intracerebral Transplantation of Porcine Choroid Plexus Provides Structural and Functional Neuroprotection in a Rodent Model of Stroke
Cesar V. Borlongan PhD*;
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