Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic Neuropeptides Across the Blood Brain Barrier.
Neurosurgery
; 78(3): 448-57; discussion 457, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26352099
ABSTRACT
BACKGROUND:
The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier.OBJECTIVE:
To test the feasibility of using nasal mucosal graft reconstruction of arachnoid defects to deliver glial-derived neurotrophic factor (GDNF) for the treatment of Parkinson disease in a mouse model.METHODS:
The Institutional Animal Care and Use Committee approved this study in an established murine 6-hydroxydopamine Parkinson disease model. A parietal craniotomy and arachnoid defect was repaired with a heterotopic donor mucosal graft. The therapeutic efficacy of GDNF (2 µg/mL) delivered through the mucosal graft was compared with direct intrastriatal GDNF injection (2 µg/mL) and saline control through the use of 2 behavioral assays (rotarod and apomorphine rotation). An immunohistological analysis was further used to compare the relative preservation of substantia nigra cell bodies between treatment groups.RESULTS:
Transmucosal GDNF was equivalent to direct intrastriatal injection at preserving motor function at week 7 in both the rotarod and apomorphine rotation behavioral assays. Similarly, both transmucosal and intrastriatal GDNF demonstrated an equivalent ratio of preserved substantia nigra cell bodies (0.79 ± 0.14 and 0.78 ± 0.09, respectively, P = NS) compared with the contralateral control side, and both were significantly greater than saline control (0.53 ± 0.21; P = .01 and P = .03, respectively).CONCLUSION:
Transmucosal delivery of GDNF is equivalent to direct intrastriatal injection at ameliorating the behavioral and immunohistological features of Parkinson disease in a murine model. Mucosal grafting of arachnoid defects is a technique commonly used for endoscopic skull base reconstruction and may represent a novel method to permanently bypass the blood-brain barrier.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
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Fármacos Neuroprotectores
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Trastornos Parkinsonianos
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Factor Neurotrófico Derivado de la Línea Celular Glial
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Membrana Mucosa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurosurgery
Año:
2016
Tipo del documento:
Article