OBJECTIVE: Hearing loss (HL) can have genetic causes, can be associated with aging or exposure to noise or ototoxic substances, and the aetiology can be attributed to vascular injury, trauma, tumours, infections or autoimmune response. All of these factors could be ascribed to alterations in cochlear microcirculation resulting in hypoxia. This condition can damage cochlear hair cells and neurons possibly leading to HL. Hypoxia and ischemia can then be identified as possible factors contributing to the aetiology of deafness, but they have not been experimentally studied yet. The purpose of this work is to develop animal models of ischemia and infarction suitable for the study of cochlear vascular damage, and to characterize them with electrophysiology and gene/protein expression analyses. METHODS: It was decided to monitor the effects of ischemia in thrombosis mimicked by complete temporary carotid occlusion, and in stroke mimicked by incomplete permanent left coronary artery. In particular this study focused on electrophysiology (ABR), analysis of organ of Corti and spiral ganglion structures and coagulation, oxidative stress and apoptosis pathways (Real-time PCR and immunohistochemistry). RESULTS: In our models, both infarction and ischemia cause a slight but significant hearing loss, localized at the cochlear apex. Furthermore, there is a slight induction of the coagulation cascade, both in procoagulant and anticoagulant part, and an activation of c-Jun N-terminal Kinase (JNK) that may lead to cell survival. In addition, only in the carotid ischemia the cuticular plate of outer hair cells is damaged. CONCLUSIONS: The two models of ischemia developed are suitable for the study of cochlear vascular damage, as they produce hearing loss and give modifications in coagulative, oxidative and apoptotic factors gene expression. We can therefore say that the damages taken into consideration act on the inner ear with vascular damage and oxidative mechanisms.
Sensorineural hearing loss and ischemic injury: Development of animal models to assess vascular and oxidative effects
OLIVETTO, ELENA;SIMONI, EDI;ASTOLFI, LAURA;MARTINI, ALESSANDRO
2013
Abstract
OBJECTIVE: Hearing loss (HL) can have genetic causes, can be associated with aging or exposure to noise or ototoxic substances, and the aetiology can be attributed to vascular injury, trauma, tumours, infections or autoimmune response. All of these factors could be ascribed to alterations in cochlear microcirculation resulting in hypoxia. This condition can damage cochlear hair cells and neurons possibly leading to HL. Hypoxia and ischemia can then be identified as possible factors contributing to the aetiology of deafness, but they have not been experimentally studied yet. The purpose of this work is to develop animal models of ischemia and infarction suitable for the study of cochlear vascular damage, and to characterize them with electrophysiology and gene/protein expression analyses. METHODS: It was decided to monitor the effects of ischemia in thrombosis mimicked by complete temporary carotid occlusion, and in stroke mimicked by incomplete permanent left coronary artery. In particular this study focused on electrophysiology (ABR), analysis of organ of Corti and spiral ganglion structures and coagulation, oxidative stress and apoptosis pathways (Real-time PCR and immunohistochemistry). RESULTS: In our models, both infarction and ischemia cause a slight but significant hearing loss, localized at the cochlear apex. Furthermore, there is a slight induction of the coagulation cascade, both in procoagulant and anticoagulant part, and an activation of c-Jun N-terminal Kinase (JNK) that may lead to cell survival. In addition, only in the carotid ischemia the cuticular plate of outer hair cells is damaged. CONCLUSIONS: The two models of ischemia developed are suitable for the study of cochlear vascular damage, as they produce hearing loss and give modifications in coagulative, oxidative and apoptotic factors gene expression. We can therefore say that the damages taken into consideration act on the inner ear with vascular damage and oxidative mechanisms.
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
