Kobaylarda akustik travma modelinde koklear fonksiyonlar üzerine memantin etkinliğinin araştırılması /
Yazar: BEGÜM ARDA
Danışman: DOÇ. DR. SELİS GÜLSEVEN GÜVEN
Trakya Üniversitesi / Tıp Fakültesi / Kulak Burun Boğaz Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2024
Konu: Kulak Burun ve Boğaz = Otorhinolaryngology (Ear-Nose-Throat)

Özet:
Çalışmamızda akustik travmada memantinin koruyucu etkinliğini elektrofizyolojik histopatolojik ve immünohistokimyasal olarak değerlendirmeyi amaçladık. Normal işiten 30 kobaydan 6 grup oluşturuldu. Grup 1 kontrol grubu, Grup 2 akut dönem akustik travma, Grup 3 kronik dönem akustik travma, Grup 4 akustik travma + steroid, Grup 5 akustik travma + serum fizyolojik, Grup 6 akustik travma + memantin uygulanan gruplardır. İntraperitoneal uygulama, akustik travmadan 1.5 saat önce, birer kez yapılmıştır. Akustik travma modeli 115-120 dB, 1,5-2 saat 6-10 kHz frekansta gürültü verilerek oluşturuldu. Travma sonrası 2 saat içinde, 7. gün, 14. gün, 21. gün DPOAE ve ABR ölçümleri yapıldı. Çalışma sonunda intrakardiyak kan alınıp kobaylar dekapite edildi. Baseline ölçümlerde tüm grupların bu frekanslardaki S/N-R değerleri ≥6 dB, ABR tüm frekanslarda <30 dB idi. ABR'de 5. ölçüm için 12, 16, 24 kHz'te memantin grubunun eşik değerleri akustik travma kronik dönem grubundan istatistiksel anlamlı ölçüde daha düşüktü (p<0.05) ABR eşik değeri 32 kHz'te memantin grubunda serum fizyolojik grubundan anlamlı yüksekti (p<0.05). 12, 16, 24 kHz'te steroid grubunda, akustik travma kronik dönem grubundan anlamlı düşüktü (p<0.05). ABR için; 1. ve 2. Ölçüm arasındaki değişim farkına bakıldığında, tone burst ABR'de grup 2-4 arasında 8, 12, 24, 32 kHz, Grup 2-6 arasında 16, 24, 32 kHz'te fark vardı (p<0.05). Histopatolojik incelemede spiral ganglionda nükleer dejenerasyon ve vakuolizasyon; Grup 6'da hafif derece, Grup 2, 3 ve 5'te yoğun derecedeydi. Serum prestin düzeyleri  Grup 4 ve Grup 6'da, Grup 3 ve Grup 5'ten istatistiksel anlamlı ölçüde daha yüksekti Çalışmamızın mevcut bulguları gürültüye bağlı işitme kaybında memantinin koruyucu etkisi olabileceğini düşündürektedir.

Abstract:
In our study, we aimed to evaluate the protective efficacy of memantine, an NMDA receptor antagonist, in acoustic trauma electrophysiologically, histopathologically and immunohistochemically. 30 adult pigmented hartley strain guinea pigs with normal hearing were randomly divided into 6 groups. Group 1 was control group, Group 2 was acute acoustic trauma, Group 3 was chronic acoustic trauma, Group 4 was acoustic trauma + steroid, Group 5 was acoustic trauma + saline, Group 6 was acoustic trauma + memantine. The applications were performed intraperitoneally, 1.5 hours before acoustic trauma, once. Acoustic trauma model was created by applying noise at a frequency of 6-10 kHz for 1.5-2 hours with a standardised noise level of 115-120 dB. ABR and DPOAE measurements were performed within 2 hours, 7 days, 14 days and 21 days after the trauma application. At the end of the study, the guinea pigs were decapitated after intracardiac blood sampling and temporal bones were examined under light and electron microscopy.
When baseline measurements were analysed, mean S/N-R values of all groups at these frequencies were ≥6 dB and ABR was <30 dB at all frequencies. In all study groups, a decrease in DPOAE SNR and an increase in Click and tone burst ABR thresholds were observed after noise application. The threshold values of the memantine group were statistically significantly lower than the acoustic trauma chronic period group at 12, 16, 24 kHz for the 5th measurement in ABR. ABR threshold value at 32 kHz was significantly higher in the memantine group than in the saline group (p<0.05). At 12, 16, 24 kHz, acoustic trauma was significantly lower in the steroid group than in the chronic period group (p<0.05). There was also a significant difference between groups 3-6 at 24 kHz (p<0.05). For ABR; when the difference in change between 1st and 2nd measurement was analysed, there was a significant difference in tone burst ABR between groups 2-4 at 8, 12, 24, 32 kHz and between groups 2-6 at 16, 24, 32 kHz (p<0.05). On histopathological examination, nuclear degeneration and vacuolisation in the spiral ganglion were mild in Group 6 and severe in Groups 2, 3 and 5. Serum prestin levels were significantly higher in Group 4 and Group 6 than in Group 3 and Group 5. Serum ribeye level was statistically significantly lower in Group 6 than in Group 3.
In the light of the present findings of our study, it is suggested that memantine may have a protective effect in noise-induced hearing loss. Further studies on this subject will contribute to the development of new clinical strategies by understanding the molecular mechanisms more clearly.