Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes

Ali Mehanna; Emanuela Szpotowicz; Melitta Schachner; Igor Jakovcevski

doi:10.1016/j.expneurol.2014.06.012

Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes

Ali Mehanna, Emanuela Szpotowicz, Melitta Schachner, Igor Jakovcevski

Rutgers, The State University

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination.

Original language	American English
Pages (from-to)	147-155
Number of pages	9
Journal	Experimental Neurology
Volume	261
DOIs	https://doi.org/10.1016/j.expneurol.2014.06.012
State	Published - Nov 2014

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

Keywords

B- and T-lymphocytes
Excitatory and inhibitory synapses
Femoral nerve
Injury
Locomotion
Mouse
Myelination
Preferential motor reinnervation
Recombination activating gene 2

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10.1016/j.expneurol.2014.06.012

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title = "Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes",

abstract = "The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination.",

keywords = "B- and T-lymphocytes, Excitatory and inhibitory synapses, Femoral nerve, Injury, Locomotion, Mouse, Myelination, Preferential motor reinnervation, Recombination activating gene 2",

author = "Ali Mehanna and Emanuela Szpotowicz and Melitta Schachner and Igor Jakovcevski",

note = "Funding Information: We are very grateful to Dr. Rudolf Martini for his comments on the manuscript. Melitta Schachner is supported by the New Jersey Commission for Spinal Cord Research and the Li Ka-Shing Foundation at the Shantou University Medical College.",

year = "2014",

month = nov,

doi = "10.1016/j.expneurol.2014.06.012",

language = "American English",

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AU - Mehanna, Ali

AU - Szpotowicz, Emanuela

AU - Schachner, Melitta

AU - Jakovcevski, Igor

N1 - Funding Information: We are very grateful to Dr. Rudolf Martini for his comments on the manuscript. Melitta Schachner is supported by the New Jersey Commission for Spinal Cord Research and the Li Ka-Shing Foundation at the Shantou University Medical College.

PY - 2014/11

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N2 - The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination.

AB - The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination.

KW - B- and T-lymphocytes

KW - Excitatory and inhibitory synapses

KW - Femoral nerve

KW - Injury

KW - Locomotion

KW - Mouse

KW - Myelination

KW - Preferential motor reinnervation

KW - Recombination activating gene 2

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C2 - 24967682

SN - 0014-4886

VL - 261

SP - 147

EP - 155

JO - Experimental Neurology

JF - Experimental Neurology

ER -

Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes

Abstract

ASJC Scopus subject areas

Keywords

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