Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic Neuropeptides Across the Blood Brain Barrier

Neurosurgery
Benjamin S BleierXue Han

Abstract

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. 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. 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. Transmucosal GDNF was equivalent to direct intrastriatal injection at preserving motor function at week 7 in both the rotarod and apomorphine rotation behavioral assays. S...Continue Reading

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Aug 19, 2018·The European Journal of Neuroscience·Enrico Bagnoli, Una FitzGerald
Feb 7, 2020·Expert Opinion on Drug Delivery·Smrithi PadmakumarMansoor M Amiji
Nov 23, 2021·Nanomedicine·Anisha A D'SouzaMansoor M Amiji

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