Hearing loss and cochlear damage in experimental pneumococcal meningitis, with special reference to the role of neutrophil granulocytes.
Hearing loss is a well-known sequelae from meningitis, affecting up to 25% of survivors. However, the principal components of the infectious and inflammatory reaction responsible for the sensorineural hearing loss remain to be identified. The present study aimed to investigate the impact of an augmented neutrophil response on the development of hearing loss and cochlear damage in a model of experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage were assessed by distortion product oto-acoustic emissions (DPOAE), auditory brainstem response (ABR) and histopathology in rats treated with ceftriaxone 28 h after infection. Rats were treated with Granulocyte Colony Stimulating Factor (G-CSF) initiated prior to infection, 28 h after infection or with ceftriaxone only. Rats were followed for 7 days, and assessment of hearing was performed before infection and 24 h and day 8 after infection. Pretreatment with G-CSF increased hearing loss 24 h after infection and on day 8 compared to untreated rats (Mann-Whitney, P = 0.012 and P = 0.013 respectively). The increased sensorineural hearing loss at day 8 was associated with significantly decreased spiral ganglion cell counts (P = 0.0006), increased damage to the organ of Corti (P = 0.007), increased areas of inflammatory infiltrates (P = 0.02) and increased white blood cell (WBC) counts in cerebrospinal fluid on day 8 after infection (P = 0.0084). Initiation of G-CSF 28 h after infection did not significantly affect hearing loss or cochlear pathology compared to controls. In conclusion, the inflammatory host reaction contributes significantly to the development of hearing loss in experimental meningitis.
Brandt
C T
CT
National Center for Antimicrobials and Infection Control, Division of Microbiology, Statens Serum Institut, Copenhagen, Denmark. ctb@ssi.dk
Cayé-Thomasen
P
P
Lund
S P
SP
Worsøe
L
L
Ostergaard
C
C
Frimodt-Møller
N
N
Espersen
F
F
Thomsen
J
J
Lundgren
J D
JD
D000818:Animals; D001933:Brain Stem / Q000473:pathology; D003051:Cochlea / Q000473:pathology*; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006098:Granulocytes / Q000473:pathology*; D034381:Hearing Loss / Q000473:pathology / Q000503:physiopathology*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D013216:Reflex, Startle
D016179:Granulocyte Colony-Stimulating Factor