Modulation of Macrophage and Microglial Responses to Axonal Injury in the Peripheral and Central Nervous Systems

Modulation of Macrophage and Microglial Responses to Axonal Injury in the Peripheral and Central... AbstractOBJECTIVE:After axonal injury, macrophages rapidly infiltrate and become activated in the mammalian peripheral nervous system (PNS) but not the central nervous system (CNS). We used the dorsal root pathway to study factors that modulate the response of macrophages to degenerating axons in both the PNS and the CNS.METHODS:Lewis rats underwent transection of dorsal roots (Group I), stab within the spinal cord (Group II), crush at the dorsal root entry zone (Group III), transection of dorsal roots combined with a CNS lesion (Group IV), or systemic administration of a known activator of macrophages, lipopolysaccharide, alone (Group V) or combined with transection of dorsal roots (Group VI). ED-1 antibody stained for macrophages and activated microglia at 7, 14, and 42 days postinjury.RESULTS:At early time points, Group I demonstrated ED-1 cells in the PNS but not the CNS portion of the degenerating dorsal roots. Group II revealed ED-1 cells near the stab lesion. Group III demonstrated ED-1 cells adjacent to the dorsal root entry zone crush site. Group IV revealed ED-1 cells along both the PNS and the CNS portions of the degenerating dorsal roots when the CNS lesion was placed near the transected roots. Group V demonstrated few ED-1 cells in the PNS and the CNS, whereas Group VI revealed a marked ED-1 cellular response along both the PNS and the CNS portions of the transected dorsal roots.CONCLUSION:Local CNS trauma and systemic administration of lipopolysaccharide can “prime” macrophages/ microglia, resulting in an enhanced response to degenerating axons in the CNS. Such priming might prove useful in promoting axonal regeneration. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Modulation of Macrophage and Microglial Responses to Axonal Injury in the Peripheral and Central Nervous Systems

Modulation of Macrophage and Microglial Responses to Axonal Injury in the Peripheral and Central Nervous Systems

Modulation of Macrophage and M icroglial Responses to Axonal Injury in the Peripheral and Central Nervous Systems Daniel A. Lazar, M.D., Dilantha B. Ellegala, M.D., Anthony M. Avellino, M.D., Andrew T. Dailey, M.D., Kate Andrus, H.T., Michel Kliot, M.D. Department of Neurological Surgery, University of Washington, and Puget Sound Veterans Affairs Health Care System, Seattle, Washington OBJECTIVE: After axonal injury, macrophages rapidly infiltrate and become activated in the mammalian peripheral nervous system (PNS) but not the central nervous system (CNS). W e used the dorsal root pathway to study factors that modulate the response of macrophages to degenerating axons in both the PNS and the CNS. METHODS: Lewis rats underw ent transection of dorsal roots (Group I), stab within the spinal cord (Group II), crush at the dorsal root entry zone (G roup III), transection of dorsal roots combined with a CNS lesion (Group IV ), or systemic administration of a known activator of macrophages, lipopolysaccharide, alone (Group V) or combined with transection of dorsal roots (G roup V I). ED-1 antibody stained for macrophages and activated microglia at 7, 14, and 42 days postinjury. RESULTS: At early tim e points, G roup I demonstrated ED-1 cells in the PNS but not the CNS portion of the degenerating dorsal roots. G roup II revealed ED-1 cells near the stab lesion. Group III demonstrated ED-1 cells adjacent to the dorsal root entry zone crush site. Group IV revealed ED-1 cells along both the PNS and the CNS portions of the degenerating dorsal roots when the CNS lesion was placed near the transected roots. Group V demonstrated few ED-1 cells in the PNS and the CNS, whereas Group VI revealed a marked ED-1 cellular response along both the PNS and the CNS portions of the transected dorsal roots. CONCLUSION: Local CNS traum a and systemic administration of lipopolysaccharide can "p rim e" macrophages/ microglia, resulting in an enhanced response to degenerating axons in...
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Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199909000-00030
Publisher site
See Article on Publisher Site

Abstract

AbstractOBJECTIVE:After axonal injury, macrophages rapidly infiltrate and become activated in the mammalian peripheral nervous system (PNS) but not the central nervous system (CNS). We used the dorsal root pathway to study factors that modulate the response of macrophages to degenerating axons in both the PNS and the CNS.METHODS:Lewis rats underwent transection of dorsal roots (Group I), stab within the spinal cord (Group II), crush at the dorsal root entry zone (Group III), transection of dorsal roots combined with a CNS lesion (Group IV), or systemic administration of a known activator of macrophages, lipopolysaccharide, alone (Group V) or combined with transection of dorsal roots (Group VI). ED-1 antibody stained for macrophages and activated microglia at 7, 14, and 42 days postinjury.RESULTS:At early time points, Group I demonstrated ED-1 cells in the PNS but not the CNS portion of the degenerating dorsal roots. Group II revealed ED-1 cells near the stab lesion. Group III demonstrated ED-1 cells adjacent to the dorsal root entry zone crush site. Group IV revealed ED-1 cells along both the PNS and the CNS portions of the degenerating dorsal roots when the CNS lesion was placed near the transected roots. Group V demonstrated few ED-1 cells in the PNS and the CNS, whereas Group VI revealed a marked ED-1 cellular response along both the PNS and the CNS portions of the transected dorsal roots.CONCLUSION:Local CNS trauma and systemic administration of lipopolysaccharide can “prime” macrophages/ microglia, resulting in an enhanced response to degenerating axons in the CNS. Such priming might prove useful in promoting axonal regeneration.

Journal

NeurosurgeryOxford University Press

Published: Sep 1, 1999

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