Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstem with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstem and other central nervous system disorders may benefit from a similar treatment paradigm.
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http://dx.doi.org/10.3171/JNS-07/07/0190 | DOI Listing |
Adv Sci (Weinh)
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Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.
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The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China.
Chrysoeriol (CHE) is a naturally occurring compound with established anti-inflammatory and anti-tumor effects. This study examines its potential role in regulating osteoclast differentiation and activity, both of which are crucial for bone remodeling. Computational docking revealed high binding affinity between CHE and RANKL, specifically at the Lys-181 residue of RANKL, suggesting potential inhibitory interactions on osteoclastogenesis.
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Faculty of Basic Sciences, King Salman International University, South Sinai City, 46612, Egypt.
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