Systemic Immunity Influences Hearing Preservation in Cochlear Implantation

Abstract

Hypothesis To determine whether a systemic immune response influences hearing thresholds and tissue response after cochlear implantation of hearing guinea pigs. Methods Guinea pigs were inoculated with sterile antigen (Keyhole limpet hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem response thresholds were performed before implantation and 1 and 4 weeks later. Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid carboxymethylcellulose sponge and was applied to the round window for 30 minutes before electrode insertion. Normal saline was used for controls. Cochlear histology was performed at 4 weeks after implantation to assess the tissue response to implantation. To control for the effect of keyhole limpet hemocyanin priming, a group of unprimed animals underwent cochlear implantation with a saline-soaked pledget applied to the round window. Results Keyhole limpet hemocyanin priming had no significant detrimental effect on thresholds without implantation. Thresholds were elevated after implantation across all frequencies tested (2–32 kHz) in primed animals but only at higher frequencies (4–32 kHz) in unprimed controls. In primed animals, dexamethasone treatment significantly reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the more frequent observation of lymphocytes in the tissue response to the implant. Conclusion Systemic immune activation at the time of cochlear implantation broadened the range of frequencies experiencing elevated thresholds after implantation. Local dexamethasone provides partial protection against this hearing loss, but the degree and extent of protection are less compared to previous studies with unprimed animals.

Relations between cochlear histopathology and hearing loss in experimental cochlear implantation

“…The experimental groups have been described in detail previously (Table 1) (Connolly et al, 2010;Eastwood et al, 2010;James et al, 2008;Maini et al, 2009;Souter et al, 2012). In the topical dexamethasone study (James et al, 2008), a carboxylmethylcellulose hyaluronic acid polymeric pledget (SeprapackÔ, Genzyme Corporation) was loaded with 5 ml of either 2% dexamethasone phosphate or saline and placed on the round window membrane for 30 min prior to cochlear implantation.…”

“…The experimental groups described above were typified by there having been hearing protection observed at 32 kHz only. In the keyhole limpet hemocyanin (KLH) study (Souter et al, 2012), animals were injected subcutaneously with KLH at a dose of 1 mg a week prior to implantation. KLH-primed animals were then randomised to receive a 5 ml volume of either 20% dexamethasone or normal saline delivered to the round window on a Seprapak pledget for 30 min prior to cochlear implantation.…”

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

“…In experimental cochlear implantation, glucocorticosteroids applied locally to the cochlea act through anti-inflammatory, anti-apoptotic and antioxidant pathways, with direct effects upon the IHCs and OHCs observed [Dinh et al, 2008a, b;Haake et al, 2009;van De Water et al, 2010;Eshraghi et al, 2011]. Systemically administered glucocorticosteroids also act at the cochlear level [Connolly et al, 2011] but in addition are thought to reduce the activation of circulating immunecompetent cells [Souter et al, 2012].…”

Application of a TNF-alpha-inhibitor into the scala tympany after cochlear electrode insertion trauma in guinea pigs: Preliminary audiologic results

“…Compared to data from similar animal models of intracochlear trauma, this is a considerable high extent of hearing loss in comparison to earlier reports that described hearing loss within a range of 0 dB to 40 dB (Eshraghi et al, 2006(Eshraghi et al, , 2007a(Eshraghi et al, , 2013James et al, 2008;Chang et al, 2009;Eastwood et al, 2010a,b;Souter et al, 2012). However, the amount of surgical trauma has been acknowledged to be unpredictable in animal models (Eastwood et al, 2010b) as well as in humans (Carlson et al, 2011) and therefore variation to some degree is explainable.…”

“…During surgery, the electrode analogue was inserted for 3 mm through the cochleostomy alongside the direction of the scala tympani and then gently withdrawn. Although this insertion depth is the current paradigm employed in almost all previous animal studies (Eshraghi et al, 2006(Eshraghi et al, , 2007a(Eshraghi et al, , 2013Souter et al, 2012), it is considerably less than usually achieved in human patients. A typical example of a commercially available electrode array is implanted for 17.5 mm to 19.2 mm after cochleostomy and thereby occupies almost the whole basal turn (Manrique et al, 2014).…”