Intracochlear tPA infusion may reduce fibrosis caused by cochlear implantation surgery

Choong, Jessica Ky-Lee; Lo, Jonathon; Chambers, Scott; Hampson, Amy; Eastwood, Hayden; O’Leary, Stephen

doi:10.1080/00016489.2019.1587504

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Human studies have highlighted the fibrous encapsulation of the implanted electrode and suggested this occurs as a result of the foreign body response and surgical trauma [ 26 , 27 , 34 , 62 ]. Animal models of cochlear implantation also show extensive neo-ossification at the site of the cochleostomy coupled with a fibrotic sheath surrounding the electrode track [ 31 , 39 , 55 , 57 , 63 , 64 ]. Although our data show that the volume of tissue reaction did not correlate with cochleostomy size, it is likely that the cochleostomy itself induced some of the tissue reaction.…”

Section: Discussionmentioning

confidence: 99%

“…Histopathological analysis is a common qualitative method used to assess cochlear fibrosis, however this method may be subject to bias [ 34 , 35 , 52 , 53 ]. Quantitative histological assessment has been previously performed on virtual reconstruction of serial sections of cochlea [ 27 , [54] , [55] , [56] ]. While effective, this approach is labour intensive and time-consuming.…”

Section: Introductionmentioning

confidence: 99%

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Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Braack,

Miles,

Amat

et al. 2023

Heliyon

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Braack,

Miles,

Amat

et al. 2023

Heliyon

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“…In addition to steroids, our search yielded six alternative therapeutical approaches with otoprotective properties. The mechanism of action of these therapeutics included prevention of apoptosis [35,[37][38][39], inhibition of pro-inflammatory cytokines [36], stimulation of neurite growth [37][38][39], and breakdown of intracochlear thrombi [40]. In one of the studies, living stem cells producing and releasing an SGN protective factor, BDNF, was applied in order to potentially enable lifelong therapy.…”

Section: Discussionmentioning

confidence: 99%

“…While acoustic ABR thresholds shifts decreased significantly at 8, 16 and 32 kHz (p = 0.0076, p = 0.0104 and p < 0.0035, respectively), and electric ABR recordings remained lower in the treatment group (p = 0.0006), impedances increased significantly in laminin-coated electrodes compared to controls (p < 0.0001). Lastly, a research group investigated whether a fibrinolytic agent, tissue-type plasminogen activator (tPA), would impact cochlear inflammation [40]. Animals were divided into low or high trauma groups, receiving inner ear irrigations of either tPA or saline immediately after implantation.…”

Section: Non-glucocorticoidsmentioning

confidence: 99%

Inner Ear Pharmacotherapy for Residual Hearing Preservation in Cochlear Implant Surgery: A Systematic Review

et al. 2022

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Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce.

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“…Evidence from guinea pig studies has shown that systemic administration of etanercept, a TNF-a inhibitor, and lipoic acid is associated with less pronounced hearing threshold shifts after cochlear implant placement when compared with controls [46,47]. Other pharmacologic agents, such as antioxidants, thrombolytics and apoptosis inhibitors have also showed some benefit in hearing preservation in animal models [48][49][50]. To our knowledge, none of these pharmacologic agents have been tested clinically.…”

Section: Anti-inflammatory Therapeuticsmentioning

confidence: 99%

Advances in hearing preservation in cochlear implant surgery

Tarabichi

Foggia

Hansen

2021

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of review Advancements in cochlear implant surgical approaches and electrode designs have enabled preservation of residual acoustic hearing. Preservation of low-frequency hearing allows cochlear implant users to benefit from electroacoustic stimulation, which improves performance in complex listening situations, such as music appreciation and speech understanding in noise. Despite the relative high rates of success of hearing preservation, postoperative acoustic hearing outcomes remain unpredictable. Recent findings Thin, flexible, lateral wall arrays are preferred for hearing preservation. Both shortened and thin, lateral wall arrays have shown success with hearing preservation and the optimal implant choice is an issue of ongoing investigation. Electrocochleography can monitor cochlear function during and after insertion of the electrode array. The pathophysiology of hearing loss acutely after cochlear implant may differ from that involved in delayed hearing loss following cochlear implant. Emerging innovations may reduce cochlear trauma and improve hearing preservation. Summary Hearing preservation is possible using soft surgical techniques and electrode arrays designed to minimize cochlear trauma; however, a subset of patients suffer from partial to total loss of acoustic hearing months to years following surgery despite evidence of residual apical hair cell function. Early investigations in robotic-assisted insertion and dexamethasone-eluting implants show promise.

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Intracochlear tPA infusion may reduce fibrosis caused by cochlear implantation surgery

Cited by 8 publications

References 19 publications

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Inner Ear Pharmacotherapy for Residual Hearing Preservation in Cochlear Implant Surgery: A Systematic Review

Advances in hearing preservation in cochlear implant surgery

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