Pharmacokinetics of intrathecally applied BDNF and effects on spinal motoneurons
| Autor: | Falk Dittrich, James A. Miller, Anne Große-Wilde, Ute Berweiler, Qiao Yan, Michael Sendtner, Klaus V. Toyka, G. Ochs |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Chick Embryo Central nervous system disease Cerebrospinal fluid Developmental Neuroscience Neurotrophic factors Internal medicine medicine Animals Injections Spinal Brain-derived neurotrophic factor Motor Neurons Sheep Dose-Response Relationship Drug business.industry Brain-Derived Neurotrophic Factor Meninges Motor neuron Protein-Tyrosine Kinases medicine.disease Spinal cord Immunohistochemistry medicine.anatomical_structure Endocrinology nervous system Neurology Spinal Cord Trk receptor Anesthesia business |
| Zdroj: | Experimental neurology. 141(2) |
| ISSN: | 0014-4886 |
| Popis: | Brain-derived neurotrophic factor (BDNF) is a potential drug for treatment of amyotrophic lateral sclerosis. Previous studies have demonstrated little or no penetration of the blood-brain barrier by BDNF, hence systemic application does not result in significant penetration into the spinal cord to produce direct action on motoneurons. Intrathecal (i.th) application of BDNF to sheep was investigated as a mean of topical administration. After continuous infusion a caudalcranial gradient of BDNF concentration in cerebrospinal fluid (CSF) and at the meninges was observed. BDNF did not penetrate spinal parenchyma but accumulated in spinal motoneurons probably due to axonal uptake in ventral roots and subsequent retrograde transport. Spinal motoneurons showed reduced levels of tropomyosin receptor kinase (trk) B and increased levels of c-fos at high BDNF doses in comparison to treatment with saline, even after treatment periods of several months. After bolus injection and cessation of continuous delivery multiphasic reduction of the BDNF concentration in CSF was detected. Our study demonstrates that i.th. application of BDNF is feasible, setting the stage for future clinical trials. |
| Databáze: | OpenAIRE |
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