Effects of delayed brain-derived neurotrophic factor application on cochlear pathology and auditory physiology in rats.
BACKGROUND
The development and maintenance of spiral ganglion cells (SGCs) appear to be supported by neurotrophins. Removal of this support leads to their gradual degeneration. Intracochlear infusion with neurotrophins can provide trophic support to SGCs in animal deafness models if given shortly after deafening. However, it is not known whether delayed intervention will provide similar protection, which might be clinically relevant. The present research was conducted to determine the effects of brain-derived neurotrophic factor (BDNF) administration on the capacity of the peripheral processes to resprout.


METHODS
The left cochlea of 20 profoundly deafened rats, which were divided into 2 groups equally, was implanted with an electrode and drug-delivery system 30 days after deafening. Either BDNF or artificial perilymph (AP) was delivered continuously for 28 days. Electrically evoked auditory brainstem responses (EABRs) were recorded during the period. SGC body and peripheral process density were measured.


RESULTS
The EABR thresholds of AP increase continually. Those of BDNF increase slowly at the beginning then decrease, and were significantly less than those of the AP group from day 14 to 28 (P < 0.01). In terms of SGC and peripheral process density, the difference between the treated and control ears of BDNF group was clearly significant (P < 0.01), but not in AP group (P > 0.05). Analysis of the left cochlea between the two groups demonstrated that SGC/peripheral process density of the BDNF group was significantly greater than that of the AP group. Finally, a functional formula was developed relating the last EABR threshold and SGC density and process density, which was as follows: T = 466.184 - 2.71 (F.B.L).


CONCLUSIONS
Under the conditions of delayed intervention following 30 days after deafening in rats, it can be concluded that BDNF enhances SGC bodies and peripheral processes survival after differentiation and so improves auditory sensitivity. SGC peripheral processes influence the auditory sensitivity.
Song
Bing-nan
BN
Department of Otorhinolaryngology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Li
Yong-xin
YX
Han
De-min
DM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor