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Regeneration of auditory nerve following complete sectioning and intrathecal application of the IN-1 antibody

The cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of... Full description

Journal Title: Acta neurochirurgica 2002, Vol.144 (2), p.181-187
Main Author: TATAGIBA, M
Other Authors: ROSAHL, S , GHARABAGHI, A , BLÖMER, U , BRANDIS, A , SKERRA, A , SAMII, M , SCHWAB, M. E
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Wien: Springer
ID: ISSN: 0001-6268
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title: Regeneration of auditory nerve following complete sectioning and intrathecal application of the IN-1 antibody
format: Article
creator:
  • TATAGIBA, M
  • ROSAHL, S
  • GHARABAGHI, A
  • BLÖMER, U
  • BRANDIS, A
  • SKERRA, A
  • SAMII, M
  • SCHWAB, M. E
subjects:
  • Animals
  • Antibodies
  • Antibodies, Monoclonal - administration & dosage
  • Antibodies, Monoclonal - pharmacology
  • Apoptosis
  • Biological and medical sciences
  • Cochlear Nerve - immunology
  • Cochlear Nerve - pathology
  • Cochlear Nerve - physiology
  • Evoked Potentials, Auditory, Brain Stem - physiology
  • Immunoglobulin Fab Fragments
  • Injections, Spinal
  • Injuries of the nervous system and the skull. Diseases due to physical agents
  • Medical research
  • Medical sciences
  • Myelin Proteins - immunology
  • Myelin Sheath
  • Nerve Fibers - physiology
  • Rats
  • Rats, Inbred Lew
  • Regeneration
  • Rodents
  • Traumas. Diseases due to physical agents
  • Viral antibodies
ispartof: Acta neurochirurgica, 2002, Vol.144 (2), p.181-187
description: The cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of the antibody IN-1 against nerve growth inhibitory proteins for one to two weeks. An age-matched control group of rats was treated with unspecific mouse IgG antibody. Because the cochlear nerve lesions resulted in significant neuronal apoptosis of spiral ganglion cells, neurotrophin-3 (NT-3) was applied to the lesion site immediately post-injury in some rats. Electrophysiological studies were carried out by recording the brainstem auditory evoked potentials (BAEP) before and immediately after the lesion, and at regular intervals up to 2 months after injury. Cochlear nerve fibres were anterogradely traced by horseradish peroxidase (HRP) or biotinylated dextran amine (BDA) injected into the spiral ganglion. The results achieved in this study were consistent with the following conclusions: 1) transection of the adult rat cochlear nerve at the CPA results in functional deafness, disappearance of BAEP, apoptosis of parent axotomized neurons of the spiral ganglion, and interruption of labelled axons close to the lesion site; 2) NT-3 is able to partially rescue axotomized neurons of the spiral ganglion; 3) injured cochlear nerve fibres show a limited spontaneous sprouting and regrowth response which does not lead to BAEP recovery; 4) intrathecal treatment with IN-1 directed against myelin-associated neurite growth inhibitory proteins promotes significant elongation of the injured fibres; and 5) the regenerating fibres seem to navigate to correct targets, and be able to establish synaptic connections for functional recovery as depicted by BAEP examinations.
language: eng
source:
identifier: ISSN: 0001-6268
fulltext: no_fulltext
issn:
  • 0001-6268
  • 0942-0940
url: Link


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titleRegeneration of auditory nerve following complete sectioning and intrathecal application of the IN-1 antibody
creatorTATAGIBA, M ; ROSAHL, S ; GHARABAGHI, A ; BLÖMER, U ; BRANDIS, A ; SKERRA, A ; SAMII, M ; SCHWAB, M. E
creatorcontribTATAGIBA, M ; ROSAHL, S ; GHARABAGHI, A ; BLÖMER, U ; BRANDIS, A ; SKERRA, A ; SAMII, M ; SCHWAB, M. E
descriptionThe cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of the antibody IN-1 against nerve growth inhibitory proteins for one to two weeks. An age-matched control group of rats was treated with unspecific mouse IgG antibody. Because the cochlear nerve lesions resulted in significant neuronal apoptosis of spiral ganglion cells, neurotrophin-3 (NT-3) was applied to the lesion site immediately post-injury in some rats. Electrophysiological studies were carried out by recording the brainstem auditory evoked potentials (BAEP) before and immediately after the lesion, and at regular intervals up to 2 months after injury. Cochlear nerve fibres were anterogradely traced by horseradish peroxidase (HRP) or biotinylated dextran amine (BDA) injected into the spiral ganglion. The results achieved in this study were consistent with the following conclusions: 1) transection of the adult rat cochlear nerve at the CPA results in functional deafness, disappearance of BAEP, apoptosis of parent axotomized neurons of the spiral ganglion, and interruption of labelled axons close to the lesion site; 2) NT-3 is able to partially rescue axotomized neurons of the spiral ganglion; 3) injured cochlear nerve fibres show a limited spontaneous sprouting and regrowth response which does not lead to BAEP recovery; 4) intrathecal treatment with IN-1 directed against myelin-associated neurite growth inhibitory proteins promotes significant elongation of the injured fibres; and 5) the regenerating fibres seem to navigate to correct targets, and be able to establish synaptic connections for functional recovery as depicted by BAEP examinations.
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subjectAnimals ; Antibodies ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - pharmacology ; Apoptosis ; Biological and medical sciences ; Cochlear Nerve - immunology ; Cochlear Nerve - pathology ; Cochlear Nerve - physiology ; Evoked Potentials, Auditory, Brain Stem - physiology ; Immunoglobulin Fab Fragments ; Injections, Spinal ; Injuries of the nervous system and the skull. Diseases due to physical agents ; Medical research ; Medical sciences ; Myelin Proteins - immunology ; Myelin Sheath ; Nerve Fibers - physiology ; Rats ; Rats, Inbred Lew ; Regeneration ; Rodents ; Traumas. Diseases due to physical agents ; Viral antibodies
ispartofActa neurochirurgica, 2002, Vol.144 (2), p.181-187
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1ROSAHL, S
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descriptionThe cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of the antibody IN-1 against nerve growth inhibitory proteins for one to two weeks. An age-matched control group of rats was treated with unspecific mouse IgG antibody. Because the cochlear nerve lesions resulted in significant neuronal apoptosis of spiral ganglion cells, neurotrophin-3 (NT-3) was applied to the lesion site immediately post-injury in some rats. Electrophysiological studies were carried out by recording the brainstem auditory evoked potentials (BAEP) before and immediately after the lesion, and at regular intervals up to 2 months after injury. Cochlear nerve fibres were anterogradely traced by horseradish peroxidase (HRP) or biotinylated dextran amine (BDA) injected into the spiral ganglion. The results achieved in this study were consistent with the following conclusions: 1) transection of the adult rat cochlear nerve at the CPA results in functional deafness, disappearance of BAEP, apoptosis of parent axotomized neurons of the spiral ganglion, and interruption of labelled axons close to the lesion site; 2) NT-3 is able to partially rescue axotomized neurons of the spiral ganglion; 3) injured cochlear nerve fibres show a limited spontaneous sprouting and regrowth response which does not lead to BAEP recovery; 4) intrathecal treatment with IN-1 directed against myelin-associated neurite growth inhibitory proteins promotes significant elongation of the injured fibres; and 5) the regenerating fibres seem to navigate to correct targets, and be able to establish synaptic connections for functional recovery as depicted by BAEP examinations.
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1Antibodies
2Antibodies, Monoclonal - administration & dosage
3Antibodies, Monoclonal - pharmacology
4Apoptosis
5Biological and medical sciences
6Cochlear Nerve - immunology
7Cochlear Nerve - pathology
8Cochlear Nerve - physiology
9Evoked Potentials, Auditory, Brain Stem - physiology
10Immunoglobulin Fab Fragments
11Injections, Spinal
12Injuries of the nervous system and the skull. Diseases due to physical agents
13Medical research
14Medical sciences
15Myelin Proteins - immunology
16Myelin Sheath
17Nerve Fibers - physiology
18Rats
19Rats, Inbred Lew
20Regeneration
21Rodents
22Traumas. Diseases due to physical agents
23Viral antibodies
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titleRegeneration of auditory nerve following complete sectioning and intrathecal application of the IN-1 antibody
authorTATAGIBA, M ; ROSAHL, S ; GHARABAGHI, A ; BLÖMER, U ; BRANDIS, A ; SKERRA, A ; SAMII, M ; SCHWAB, M. E
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1Antibodies
2Antibodies, Monoclonal - administration & dosage
3Antibodies, Monoclonal - pharmacology
4Apoptosis
5Biological and medical sciences
6Cochlear Nerve - immunology
7Cochlear Nerve - pathology
8Cochlear Nerve - physiology
9Evoked Potentials, Auditory, Brain Stem - physiology
10Immunoglobulin Fab Fragments
11Injections, Spinal
12Injuries of the nervous system and the skull. Diseases due to physical agents
13Medical research
14Medical sciences
15Myelin Proteins - immunology
16Myelin Sheath
17Nerve Fibers - physiology
18Rats
19Rats, Inbred Lew
20Regeneration
21Rodents
22Traumas. Diseases due to physical agents
23Viral antibodies
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7SCHWAB, M. E
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atitleRegeneration of auditory nerve following complete sectioning and intrathecal application of the IN-1 antibody
jtitleActa neurochirurgica
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date2002
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volume144
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abstractThe cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of the antibody IN-1 against nerve growth inhibitory proteins for one to two weeks. An age-matched control group of rats was treated with unspecific mouse IgG antibody. Because the cochlear nerve lesions resulted in significant neuronal apoptosis of spiral ganglion cells, neurotrophin-3 (NT-3) was applied to the lesion site immediately post-injury in some rats. Electrophysiological studies were carried out by recording the brainstem auditory evoked potentials (BAEP) before and immediately after the lesion, and at regular intervals up to 2 months after injury. Cochlear nerve fibres were anterogradely traced by horseradish peroxidase (HRP) or biotinylated dextran amine (BDA) injected into the spiral ganglion. The results achieved in this study were consistent with the following conclusions: 1) transection of the adult rat cochlear nerve at the CPA results in functional deafness, disappearance of BAEP, apoptosis of parent axotomized neurons of the spiral ganglion, and interruption of labelled axons close to the lesion site; 2) NT-3 is able to partially rescue axotomized neurons of the spiral ganglion; 3) injured cochlear nerve fibres show a limited spontaneous sprouting and regrowth response which does not lead to BAEP recovery; 4) intrathecal treatment with IN-1 directed against myelin-associated neurite growth inhibitory proteins promotes significant elongation of the injured fibres; and 5) the regenerating fibres seem to navigate to correct targets, and be able to establish synaptic connections for functional recovery as depicted by BAEP examinations.
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doi10.1007/s007010200022