TY  - JOUR
A1  - Förster, Carola Y.
A1  - Shityakov, Sergey
A1  - Scheper, Verena
A1  - Lenarz, Thomas
T1  - Linking cerebrovascular dysfunction to age-related hearing loss and Alzheimer’s disease — are systemic approaches for diagnosis and therapy required?
JF  - Biomolecules
N2  - Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction, cognitive decline, and the accumulation of amyloid β peptide (Aβ) in the brain and tau-related lesions in neurons termed neurofibrillary tangles (NFTs). Aβ deposits and NFT formation are the central pathological hallmarks in AD brains, and the majority of AD cases have been shown to exhibit a complex combination of systemic comorbidities. While AD is the foremost common cause of dementia in the elderly, age-related hearing loss (ARHL) is the most predominant sensory deficit in the elderly. During aging, chronic inflammation and resulting endothelial dysfunction have been described and might be key contributors to AD; we discuss an intriguing possible link between inner ear strial microvascular pathology and blood–brain barrier pathology and present ARHL as a potentially modifiable and treatable risk factor for AD development. We present compelling evidence that ARHL might well be seen as an important risk factor in AD development: progressive hearing impairment, leading to social isolation, and its comorbidities, such as frailty, falls, and late-onset depression, link ARHL with cognitive decline and increased risk of dementia, rendering it tempting to speculate that ARHL might be a potential common molecular and pathological trigger for AD. Additionally, one could speculate that amyloid-beta might damage the blood–labyrinth barrier as it does to the blood–brain barrier, leading to ARHL pathology. Finally, there are options for the treatment of ARHL by targeted neurotrophic factor supplementation to the cochlea to improve cognitive outcomes; they can also prevent AD development and AD-related comorbidity in the future.
KW  - Alzheimer’s disease
KW  - age-related hearing loss
KW  - neurovasculature
KW  - blood–brain barrier
KW  - blood–labyrinth barrier
KW  - spiral ganglion neuron
KW  - pharmacotherapy
KW  - neurotrophic factor
KW  - inner ear
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297552
SN  - 2218-273X
VL  - 12
IS  - 11
ER  - 
TY  - JOUR
A1  - Hütten, Mareike
A1  - Dhanasingh, Anandhan
A1  - Hessler, Roland
A1  - Stöver, Timo
A1  - Esser, Karl-Heinz
A1  - Möller, Martin
A1  - Lenarz, Thomas
A1  - Jolly, Claude
A1  - Groll, Jürgen
A1  - Scheper, Verena
T1  - In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment
JF  - PLoS ONE
N2  - Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.
KW  - gels
KW  - cochlea
KW  - silicones
KW  - deafness
KW  - inner ear
KW  - drug delivery
KW  - inflammation
KW  - connective tissue
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119375
VL  - 9
IS  - 8
ER  -