Drug delivery into the peripheral nerves and nerve roots has important implications for effective local anesthesia and treatment of peripheral neuropathies and chronic neuropathic pain. Similar to drugs that need to cross the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) to gain access to the central nervous system (CNS), drugs must cross the peripheral nerve barriers (PNB), formed by the perineurium and blood-nerve barrier (BNB) to modulate peripheral axons. Despite significant progress made to develop effective strategies to enhance BBB permeability in therapeutic drug design, efforts to enhance drug permeability and retention in peripheral nerves and nerve roots are relatively understudied. Guided by knowledge describing structural, molecular and functional similarities between restrictive neural barriers in the CNS and peripheral nervous system (PNS), we hypothesize that certain CNS drug delivery strategies are adaptable for peripheral nerve drug delivery. In this review, we describe the molecular, structural and functional similarities and differences between the BBB and PNB, summarize and compare existing CNS and peripheral nerve drug delivery strategies, and discuss the potential application of selected CNS delivery strategies to improve efficacious drug entry for peripheral nerve disorders.
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http://dx.doi.org/10.1002/adtp.202200150 | DOI Listing |
ASN Neuro
January 2025
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
In light of the increasing importance for measuring myelin ratios - the ratio of axon-to-fiber (axon + myelin) diameters in myelin internodes - to understand normal physiology, disease states, repair mechanisms and myelin plasticity, there is urgent need to minimize processing and statistical artifacts in current methodologies. Many contemporary studies fall prey to a variety of artifacts, reducing study outcome robustness and slowing development of novel therapeutics. Underlying causes stem from a lack of understanding of the myelin ratio, which has persisted more than a century.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium.
View Article and Find Full Text PDFJ Neuroimaging
January 2025
Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
Intracranial pressure (ICP) monitoring is a cornerstone of neurocritical care in managing severe brain injury. However, current invasive ICP monitoring methods carry significant risks, including infection and intracranial hemorrhage, and are contraindicated in certain clinical situations. Additionally, these methods are not universally available.
View Article and Find Full Text PDFNeurosurg Rev
January 2025
Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA.
Postoperative facial nerve (FN) dysfunction is associated with a significant impact on the quality of life of patients and can result in psychological stress and disorders such as depression and social isolation. Preoperative prediction of FN outcomes can play a critical role in vestibular schwannomas (VSs) patient care. Several studies have developed machine learning (ML)-based models in predicting FN outcomes following resection of VS.
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