KISEP 흰쥐에서일측전정기관손상후전정안구반사의회복과내측전정신경핵에서 c-fos 단백질발현과의관계 * Abstract 황오성 이문영 김민선 박병림 이정헌 김종길 송영창 곽기용 Relationship between Recovery of Vestibulo

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1 KISEP 흰쥐에서일측전정기관손상후전정안구반사의회복과내측전정신경핵에서 c-fos 단백질발현과의관계 * Abstract 황오성 이문영 김민선 박병림 이정헌 김종길 송영창 곽기용 Relationship between Recovery of Vestibuloocular Reflex and c-fos Protein Expression in Medial Vestibular Nuclei Following Unilateral Labyrinthectomy in Rats Oh Seong Whang, M.D., Moon Young Lee, M.D., Min Sun Kim, M.D., Byung Rim Park, M.D. Department of Physiology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang University, Chunbuk, Korea Jung Hun Lee, M.D., Jong Kil Kim, M.D., Young Chang Song, M.D., Kee Yong Kwak, M.D. Department of Otolaryngology, Wonkwang University School of Medicine, Chunbuk, Korea Relationships between recovery of vestibuloocular reflex and expression of c-fos immunoreactive cells in the medial vestibular nuclei following unilateral labyrinthectomyulx were investigated in rats. Frequency of spontaneous nystagmus, velocity of eye movement induced by sinusoidal rotation of the whole body at frequencies of 0.1, 0.2, 0.5Hz, and the number of c-fos immunoreactive cells in the medial vestibular nuclei were measured for 72 hours after ULX. Frequency of spontaneous nystagmus was beats/secsmsd immediately after ULX and disappeared completely within 48 hours. On sinusoidal rotation, eye movement induced by rotation toward the lesioned side recovered normal pattern within 24 hours at 0.1Hz rotation, and 12 hours at 0.2, 0.5Hz. Directional preponderance which represents the symmetry of bilateral vestibular functions decreased to less than 20 at 72 hours, but did not recover normal limit. The number of c- fos immunoreactive cells in the bilateral medial vestibular nuclei was severe asymmetry till 24 hours of ULX. However, the symmetry was recovered after 48 hours. These results indicate that the 739

2 recovery of vestibuloocular reflex correlates with the expression of c-fos immunoreactive cells of the medial vestibular nuclei in the early stage of vestibular compensation following ULX. Therefore, the vestibular nuclei may play a key role in vestibular compensation. Korean J Otolaryngol 405, 1997 KEY WORDSc-Fos protein Medial vestibular nucleus Unilateral labyrinthectomy Vesti-bular compensation. 서론 실험방법 1. 실험동물 740

3 2. 전정기관의회전자극 3. 안구운동의기록및분석 Korean J Otolaryngol 405, May c-fos 면역조직화학법 741

4 실험성적 1. 일측전정기관손상후자발안진의변화 2. 일측전정기관손상후회전자극에의한전정안구반사의변화 Fig. 1. Recovery of spontaneous nystagmus following left labyrinthectomy in the same rabbit. F & S, fast and slow component of nystagmus, respectivelycontrol, before labyrinthectomy 5 min, 4 hrs, 12 hrs, 24 hrs are time after labyrinthectomy. Fig. 2. Frequency of spontaneous nystagmus in course of time following unilateral labyrinthectomy. 0 hour means the time at just after labyrinthectomy. The number of rats is 12. Values are meanssd. 742

5 Korean J Otolaryngol 405, May 1997 Fig. 4. Percent change of slow component velocity of eye movement induced by sinusoidal rotation following unilateral labyrinthectomy. INTACT, rotation toward intact sidelesion, rotation toward lesioned sidec, before labyrinthectomy100%. Negative values are out of phase in eye movement by lesioned side rotation. Fig. 3. Recovery of eye movement induced by sinusoidal rotation at 0.2 Hz following left labyrinthectomy in the same rat. POSITION, position curve; R L, rightward and leftward rotation, respectively. Other notations are as in the previous figures. Fig. 5. Directional preponderance of vestibuloocular reflex induced by sinusoidal rotation following unilateral labyrinthectomy. Maximum value includes more than 100%. Values are meanssd. 743

6 한이인지 제 4 0 권 제 5 호 1997 Fig. 6. Photographs of c-fos immunoreactive cells in the bilateral medial vestibular nuclei following left labyrinthectomy. CON, before labyrinthectomy; R & L, right and left medial vestibular nuclei, respectively. Asymmetry of c-fos expression in bilateral medial vestibular nuclei is shown at hours 2 and 24 after labyrinthectomy, but symmetry is accomplished at hour 48 after labyrinthectomy. 744

7 Fig. 7. Number of c-fos immunoreactive cells in the bilateral medial vestibular nuclei following unilateral labyrinthectomy. INTACT, intact side medial vestibular nuclei, LESION, lesioned side medial vestibular nuclei. Values are meanssd. *p0.05, **p 일측전정기관손상후 c-fos 단백질발현 Korean J Otolaryngol 405, May 1997 고안 745

9 결론 Korean J Otolaryngol 405, May 1997 References 1) Akaike T, Fanardjian VV, Tto M, Ohno T, et al: Cerebellar control of vestibulospinal tract cell in rabbit. Exp Brain Res. 18: ) Bao J, Reier PJ, Munson JB, et al:enhancement of c-fos expression in neurons of the rat spinal cord after partial denervation:evidence for functional plasticity. Exp Neurol. 1993;122: ) Barber HO, Stockwell CW:Manual of electronystagmography. The CV Mosby Co:St Louis, ) Cirelli C, Pompeiano M, D Ascanio P, Arrighi P, Pompeiano O:c-Fos expression in the rat brain after unilateral labyrinthectomy and its relation to the uncompensated and compensated stages. Neuroscience. 1996;70: ) Dragunow M, Faull R:The use of c-fos as a metabolic marker neuronal pathway tracing. J Neurosci Methods. 1989;29: ) Draisci G, Iadarola MJ:Temporal analysis of increases in c-fos preprodynorph in and preproenkephalin in mrna s in rat spinal cord. Mol Brain Res 1989;6: ) Fisch U:The vestibular response following unilateral vestibular neurectomy. Acta Otolaryngol. 1973;76: ) Fuller JH:The dynamic neck-eye reflex in mammals. Exp Brain Res. 1980;41: ) Hikosaka O, Maeda M:Cervical effects on abducens motoneurons and this interaction with vestibuloocular reflex. Exp Brain Res. 1973;18:

10 ) Ishikawa K, Togawa K:Effect of blindfolding one eye on vestibular compensation in guinea pigs. Acta Otolaryngol Suppl. 1988;447: ) Jensen DW:Survival of function in the deafferented vestibular nerve. Brain Res. 1983;273: ) Kaufman GD, Anderson JH, Beitz AJ, et al:fosdefined activity in rat brainstem following centripetal acceleration. J Neurosci. 1992;12: ) Kim JH, Park BR, Park CS, et al:studies on the interrelationship between the vestibular semicircular canals and the extrocular muscles in rabbits and cats. Korean J Physiol. 1987;21: ) Llinas R, Precht W, Clarke M, et al:cerebellar Purkinje cell responses to physiological stimulation of the vestibular system in the frog. Exp Brain Res. 1971;13: ) Markham CH, Yagi T, Curthoys IS, et al:the contribution of the contralateral labyrinth to second order vestibular neuronal activity in the cat. Brain Res. 1977;138: ) Mendell LM:Modifiability of spinal synapses. Physiol Rev. 1984;64: ) Morgan JI, Curran T:Stimulus-transcription coupling in the nervous system:involvement of the induci-ble proto-oncogenes fos and jun. Annu Rev Neurosci. 1991;14: ) Newlands SD, Perachio AA:Compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in decerebrated gerbil. Exp Brain Res. 1990;82: ) Park BR, Kim MS, Jeong JY, Lee JH, et al:recovery of acute vestibular symptoms following unilateral labyrinthectomy in rabbits. Society for Neuroscience Abst. 1993;60:4 20) Park BR, Park CS:Cervico-ocular reflex in bilateral labyrinthectomized cats. Kor J Physiol a;22: ) Park BR, park HA:A study of thu sinusoidal head rotator. Channam Med J. 1988b;25: ) Park BR, Suh JS, Kim MS, Jeong JY, Chun SW, Lee JH:Influence of sensory deprivation or electrical stimulation on acute vestibular symptoms follwing unilateral labyrinthectomy in rabbits. Acta Otolaryngol Suppl ;19: ) Precht W, Shimazu H, Markham CH, et al:a mechanism of central compensation of vestibular function follwing hemilabyrinthectomy. J Neurophysiol. 1966;29: ) Schaefer KP, Meyer DL:Compensation of vestibular lesion. In:Handbook of sensory physiology, edited by HH Kornhuber. Springer:Berlin. 1974: ) Sekitani T:Current data on vestibular neuronitis. Pract Otol(Kyoto). 1988;81: ) Sharp FR, Sagar SM, Hicks K, Lowenstein D, Hisanaga K, et al:c-fos messenger RNA, fos, and fos-related antigen induction by hypertonic saline and stress. J Neurosci. 1991;11: ) Smith PF, Curthoy IS:Mechanisms of recovery following unilateral labyrinthectomy:a review. Brain Res Rev. 1989;14: ) Smith PF, Curthoys IS:Neuronal activity in the contralateral medial vestibular nucleus of the guinea pig following unilateral labyrinthectomy. Brain Res. 1988a;444: ) Smith PF, Curthoys IS:Neuronal activity in the ipsilateral medial vestibular nucleus of the guinea pig follwing unilateral labyrinthectomy. Brain Res. 1988b;444: ) Smith PF, Darlington CL, Curthoys IS, et al:the effect of visual deprivation on vestibular compensation in the guinea pig. Brain Res. 1986;36 4: ) Snow PJ, Wilson P:Blind axonal endings and plasticity in the mammalian CNS. News Physiol Sci, 1990;5: ) Szentagothai J:The elementary vestibulo-ocular arc. J Neurophysiol. 1950;13: ) Wilson VJ, Melvill Jones G:Mammalian vestibular physiology. Plenum Press:New York, ) Wilson VJ, Schor RH, Suzuki I, Park BR, et al: Spatial organization of neck and vestibular reflexes acting on the forelimbs of the decerebrate cat. J Neurophysiol. 1986;55: ) Zennou-Azogui Y, Xerri C, Harlay F, et al:visual sensory substitution in vestibular compensation:neuronal substrated in the alert cat. Exp Brain Res. 1994;98:

975_983 특집-한규철, 정원호

975_983 특집-한규철, 정원호 Focused Issue of This Month Gyu Cheol an, MD Department of Otolaryngology ead & Neck Surgery, Gachon University of College Medicine E - mail : han@gilhospital.com Won-o Jung, MD Department of Otolaryngology