4.7 Article

Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys

Journal

NEUROBIOLOGY OF DISEASE
Volume 23, Issue 2, Pages 471-480

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.04.014

Keywords

choroid plexus; CNS transplantation; alginate; encapsulation; neuroprotection

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Huntington's disease (HD) results from degeneration of striatal neurons. Choroid plexus (CP) cells secrete neurotrophic factors, and CP transplants are neuroprotective in rat models of HD. To determine if similar neuroprotective effects could be obtained in primates, porcine CP was encapsulated in alginate capsules. PCR confirmed that the CP cells expressed transthyretin and immunocytochemistry demonstrated typical ZO-1 and tubulin staining. In vitro, CP conditioned media enhanced the survival and preserved neurite number and length on serum deprived neurons. Cynomolgus primates were transplanted with CP-loaded capsules into the caudate and putamen followed by quinolinic acid (QA) lesions 1 week later. Control monkeys received empty capsules plus QA. Choroid plexus transplants significantly protected striatal neurons as revealed by stereological counts of NeuN-positive neurons (8% loss vs. 43% in controls) and striatum volume (10% decrease vs. 40% in controls). These data indicate that CP transplants might be useful for preventing the degeneration of neurons in HD. (c) 2006 Elsevier Inc. All rights reserved.

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