| Autor: |
Whitesell, L, Geselowitz, D, Chavany, C, Fahmy, B, Walbridge, S, Alger, J R, Neckers, L M |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; May 1993, Vol. 90 Issue: 10 p4665-4669, 5p |
| Abstrakt: |
We report experiments in the rat demonstrating the feasibility of intraventricular administration of oligodeoxynucleotides (ODNs) as a regional treatment approach to disorders within the central nervous system (CNS). Although we find little intrinsic nuclease activity in cerebrospinal fluid (CSF), phosphodiester ODNs are rapidly degraded by brain-associated alpha-exonuclease activity. Phosphorothioate ODNs, however, appear resistant to degradation in the CNS and, after intraventricular administration, we find they are cleared in a manner consistent with CSF bulk flow. Continuous infusion of ODN at 1.5 nmol/hr by miniosmotic pump can maintain micromolar concentrations of intact phosphorothioate ODN in CSF for at least 1 week without obvious neurologic or systemic toxicity. After infusion, extensive brain penetration and marked cellular uptake, especially by astrocytic cells, is demonstrated. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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