Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria.
BACKGROUND
Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the stria vascularis, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment.


METHODS
The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier.


RESULTS
Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals.


CONCLUSIONS
Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria.
Department of Otorhinolaryngology, Innsbruck Medical University, Anichstraβe 35, 6020 Innsbruck, Austria. Joachim.Schmutzhard@i-med.ac.at
Joachim
J
Schmutzhard
Christian H
CH
Kositz
Rudolf
R
Glueckert
Erich
E
Schmutzhard
Annelies
A
Schrott-Fischer
Peter
P
Lackner
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000032:analysis; D000072259:Connexin 26; D017630:Connexins / Q000032:analysis; D004195:Disease Models, Animal; D034381:Hearing Loss / Q000209:etiology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D007759:Labyrinth Diseases / Q000473:pathology*; D016779:Malaria, Cerebral / Q000150:complications* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D055493:Spiral Ligament of Cochlea / Q000473:pathology*
D017630:Connexins; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26; D053148:Caspase 3