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IPOACUSIA NEUROSENSORIALE E DANNO ISCHEMICO. MESSA A PUNTO DI UN MODELLO ANIMALE PER VALUTARNE GLI EFFETTI VASCOLARI E OSSIDATIVI.
No full textHearing impairment is an increasingly common disease. In Italy deaf people are about
seven million, including half a million adults with disabling hearing loss and over one
thousand births per year with congenital deafness. This causes difficulty in integration in
society for adults and prevents the language acquisition for children (Fekete, 1999).
As hearing loss has high social costs, the expectation for the development of new
treatments is extensive and diseases leading to hearing damage are increasingly studied
from clinic and base research. 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. For this reason 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
the analysis of: organ of Corti and spiral ganglion structures, coagulation, oxidative stress
and apoptosis.
A further aim was to compare these models with other models of ototoxic damage, such as
noise and cisplatin. These models are both characterized for electrophysiology, oxidative
stress and apoptosis, but the possible involvement of vascular damage has not been
investigated yet. This comparison helped us to characterize the new models of vascular
injury in the oxidation and apoptosis expression patterns.
In our models, both infarction and ischemia cause a small 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 JNK, that may
lead to cell survival. In addition, only in the carotid ischemia the cuticular plate of outer hair
cells is damaged.
Even noise and cisplatin cause vascular damage, but while in noise-treated animals the
coagulation genes show only an mRNA expression increase, after cisplatin administration
an mRNA and protein increase of the tissue factor is detected, which leads to the
coagulation cascade activation. In the ischemic models we did not detect any apoptosis
activation, while in the other models we noticed opposite reactions: in noise there is an
increased transcription of the anti-apoptotic genes that leads to cell survival, while cisplatin
activates pro-apoptotic factors. The activation of apoptosis is documented in literature and
is confirmed in both conditions by OHC loss detected in histological sections, which leads to
a more severe deafness than in the ischemia models.
In conclusion, the two models of ischemia developed are suitable for the study of cochlear
vascular damage, as they produce a slight hearing loss and give modifications in
coagulative, oxidative and apoptotic factors gene expression. Furthermore, the comparison
with two other widely used models allowed us to specify the pathways involved.
We can therefore say that all types of damage taken into consideration act on the inner ear
with vascular damage and oxidative mechanisms
Effetti di ischemia, rumore e cisplatino sull'orecchio interno-Ipoacusia da danno neurosensoriale: uno studio sperimentale sul ratto
No full textProduction of reactive oxygen species in microsomes from peripheral blood mononuclear cells of patients affected by allergic asthma
No full textProduction of reactive oxygen species in microsomes isolated from peripheral blood mononuclear cells of patients affected by allergic asthma
No full textSensorineural hearing loss and ischemic injury: Development of animal models to assess vascular and oxidative effects
No full textHearing loss may be genetic, associated with aging or exposure to noise or ototoxic substances. Its aetiology can be attributed to vascular injury, trauma, tumours, infections or autoimmune response. All these factors could be related to alterations in cochlear microcirculation resulting in hypoxia, which in turn may damage cochlear hair cells and neurons, leading to deafness. Hypoxia could underlie the aetiology of deafness, but very few data about it are presently available. The aim of this work is to develop animal models of hypoxia and ischemia suitable for study of cochlear vascular damage, characterizing them by electrophysiology and gene/protein expression analyses. The effects of hypoxia in infarction were mimicked in rat by partial permanent occlusion of the left coronary artery, and those of ischemia in thrombosis by complete temporary carotid occlusion. In our models both hypoxia and
ischemia caused a small but significant hearing loss, localized at the cochlear apex. A slight induction of the coagulation cascade and of oxidative stress pathways was detected as cell survival mechanism, and cell damages were found on the cuticular plate of outer hair cells only after carotid ischemia. Based on these data, the two developed models appear suitable for in vivo studies of cochlear vascular damage
Morphological and functional structure of the inner ear: Its relation to Ménière's disease
No full textMénière's disease is a disabling disorder presenting with crises of aural fullness, tinnitus, hearing loss and vertigo. The hallmark of the pathology is a labyrinthine hydrops, but its pathogenesis remains unclear. This unknown aetiology explains the lack of a good pharmacological treatment. Here, we wish to evaluate the different parameters that can be involved in the progression of the disease, focusing on vascular disorders, production of reactive oxygen species and the relationship between the endolymph and haematic perfusion. We know that the blood supply must be adequate to guarantee the establishment of the endocochlear potential and the production of endolymph, so aberrant microcirculation may be an aetiological factor for Méniè re's disease. © 2012 Informa Healthcare
Vascular and oxidative damage underlying sensorineural hearing loss in rat animal model.
No full textDo ischemia, noise and cisplatin cause cochlear vascular damage?
No full textDeafness is one of the most commonly diffused disabilities because of increasing people
age and environmental noise levels. Hearing damage caused by age, noise or ototoxic
drugs is generally irreversible since cochlear neurons and hair cells are not able to
regenerate.
Noise-induced hearing loss and ototoxic drugs are significant sources of hearing
impairment among humans. The causing mechanisms can be attributed to: direct
mechanical damage and damage caused by metabolic stress, mediated by an increased
of the oxidative metabolism in the inner ear. It has already been observed that routine
blood pressure values recorded in young adult patients complaining of sudden
sensorineural hearing loss have been significantly lower when compared with those of
an age-matched control group, thus indicating a possible role of hypothension in the
genesis of inner ear disorders. For the study of sudden hearing loss, in literature are
available several in vivo protocols for deafening noise and ototoxic drugs and few in vitro
for hipoxic damage.
This research aims to develop in rat model, the techniques to induce damages to inner
ear following ischemic events like hypoxia, deafening noise or cisplatin toxicity, and to
investigate in deep the amount of damage.
The preliminary histological results allowed us to detect a specific protein expression
profile in relation to the tissue oxidation (HIF-1á, p-JNK) and cardiovascular disease (TM
and TF). This profile, in conclusion, shows a correlation among the three different
hearing loss damages: they cause vascular damage
Functional and Morphological characterization of NOD-SCID inner ear
No full textOBJECTIVE. Sensorineural hearing impairment is a consequence of hair cells (HC) and/or spiral ganglion neurons loss. In mammals, HCs are unable to regenerate, so their loss cause irreversible damages. For this reason it is very important to study the mechanisms to stimulate cochlear tissues regeneration with stem cells. Moreover it is necessary to choose the correct animal model. The NOD-SCID is a mouse with hampered immune system useful for stem cells transplantation, but there are no information about its auditory capacity. The aim of the project is to characterize the functionality and the morphology of the NOD-SCID inner ear because it derives from NOD mouse which presents a progressive hearing loss.
METHODS. Animal models: 4-8-12 week-old CBA/J (non hearing-impaired), NOD (hearing-impaired) and NOD-SCID. Investigations: electrophysiology (ABR), histology of cochlea, spleen and tongue. All tissues were fixed, paraffin-embedded, and the sections were Hematoxylin-Eosin stained. The cochleae were cut into ten series of slides with sequential sections (thick 5um), for each section we evaluated inner and outer hair cells number, neuronal density, stria vascularis (SV) area and spiral ligament (SL) area. The percentage of fungiform and filiform papillae was counted along the superficial side of the tongue sections (1). The morphological changes of red and white pulp of the spleen were studied. All data were analyzed with ANOVA Bonferroni’s test.
RESULTS. NOD-SCID mice show a progressive hearing impairment at high frequencies from 4 to 12 weeks. The deafness appears to be associated with hair cells loss in the medium/basal region of the cochlea, likely as a consequence of SV and SL morphological and functional alterations. The histological study of NOD-SCID tongue demonstrates abnormalities in the organ development and an erythroid cells accumulation is observed in the spleen red pulp.
CONCLUSIONS. Deafness of NOD-SCID mice could be due to premature aging, or could be a consequence of physiological/metabolic alterations that interfere with Organ of Corti functionality causing hair cells death
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