Activated Macrophage/Microglial Cells Can Promote the Regeneration of Sensory Axons into the Injured Spinal Cord

Prewitt, Chantal; Niesman, Ingrid R.; Kane, Cynthia J.M.; Houlé, John D.

doi:10.1006/exnr.1997.6694

Cited by 245 publications

(136 citation statements)

References 54 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Astrogliosis is a hallmark of wound healing, since astrocytes are the main source of neuroprotective/neurotrophic compounds in the CNS (Martin, 1992;Ridet et al, 1997;Yoshida and Toya, 1997), while neovascularization is fundamental to re-establish blood supply and reduce secondary anoxic/hypoxic damage. Finally, there is increasing evidence about a neurotrophic/neuroprotective action of microglia/macrophages (Elkabes et al, 1996;Zietlow et al, 1999;Rabchevsky and Streit, 1997;Chamak et al, 1994;Prewitt et al, 1997;Suzuki et al, 2001;Polazzi et al, 2001). On this basis, therapeutic strategies directed to reducing secondary neuronal damage should be preferably designed not to reduce the microglia/macrophage reaction per se but rather to specifically inhibit the detrimental activities of reactive microglia/macrophages.…”

Section: Proliferative Origin and Fate Of Microgliamentioning

confidence: 99%

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Vela

Yáñez

González

et al. 2002

Journal of Neurotrauma

View full text Add to dashboard Cite

Ablation of the hindlimb area of the sensorimotor cortex produces degeneration in the cortex (invasive traumatic injury) and leads to retrograde and/or anterograde degeneration in the thalamus (non-invasive injury, distal reaction). This provides an useful model to study the proliferation and elimination of microglia/macrophages in different neurodegenerative conditions. Changes in the morphology, distribution and numbers of microglia in the affected cortex and thalamus were analyzed at various time points (12 h to 30 days) after injury. In parallel, proliferation was determined by immunocytochemistry for the proliferating cell nuclear antigen and cell death by the TUNEL method. Proliferation was an early event in the microglia/macrophage response (from 12 h in the cortex and from 2 days post-lesion in the thalamus) and persisted up to 30 days. The different microglia/macrophage phenotypes proliferated in a specific temporospatial pattern. In the lesioned cortex, early activation and proliferation of intrinsic microglia was accompanied, from the second post-lesion day, by monocyte entrance and proliferation of monocyte-derived cells. In contrast, accumulation of cells in the thalamus resulted from proliferation of intrinsic microglia, without apparent/significant monocytic recruitment. During the subsequent microglia/macrophages removal the majority of the cells in the cortex transformed into ameboid cells devoid of cell processes that progressively accumulated as fully-developed macrophages tissue within the lesion (3-14 days) ultimately migrating out to the meningeal connective tissue (14-30 days). Only some process-bearing cells, remaining in the cortical tissue bordering the lesion, underwent degeneration by 14-21 days post-lesion. In contrast, in the distal affected thalamic nuclei, microglial cell death occurred by 14-30 days post-lesion. Altogether, this study shows that both the origin and fate of microglia/ macrophages depend on the nature of the lesion.

show abstract

Section: Proliferative Origin and Fate Of Microgliamentioning

confidence: 99%

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Vela

Yáñez

González

et al. 2002

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…Some of the more frequently used cellular interventions have employed fibroblasts (40, 49,59,95,104), been demonstrated to facilitate long-tract regeneration and behavioral recovery in a number of SCI paradigms embryonic stem cells (60,63,100), bone marrow stromal cells (13, 45,61,70), fetal tissue (3), peripheral nerve (9, 29,56,78,79,89). Recent advances in tissue culturing procedures have shown the potential of OEG to be hargrafts (18,19,82), macrophages (34, 77,94), Schwann cells (10,11,72,73,97), and olfactory ensheathing glia vested from either the olfactory bulb (89) or nasal mucosa for autologous transplantation into a spinal cord-(9, 32,78,79,89), often in combination with molecular or pharmacological strategies aimed at increasing neuroinjured individual.…”

Section: Introductionmentioning

confidence: 99%

Survival, Integration, and Axon Growth Support of Glia Transplanted into the Chronically Contused Spinal Cord

et al. 2005

View full text Add to dashboard Cite

Due to an ever-growing population of individuals with chronic spinal cord injury, there is a need for experimental models to translate efficacious regenerative and reparative acute therapies to chronic injury application. The present study assessed the ability of fluid grafts of either Schwann cells (SCs) or olfactory ensheathing glia (OEG) to facilitate the growth of supraspinal and afferent axons and promote restitution of hind limb function after transplantation into a 2-month-old, moderate, thoracic (T8) contusion in the rat. The use of cultured glial cells, transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP), permitted long-term tracking of the cells following spinal cord transplantation to examine their survival, migration, and axonal association. At 3 months following grafting of 2 million SCs or OEG in 6 µl of DMEM/F12 medium into the injury site, stereological quantification of the three-dimensional reconstructed spinal cords revealed that an average of 17.1 ± 6.8% of the SCs and 2.3 ± 1.4% of the OEG survived from the number transplanted. In the OEG grafted spinal cord, a limited number of glia were unable to prevent central cavitation and were found in patches around the cavity rim. The transplanted SCs, however, formed a substantive graft within the injury site capable of supporting the ingrowth of numerous, densely packed neurofilament-positive axons. The SC grafts were able to support growth of both ascending calcitonin gene-related peptide (CGRP)-positive and supraspinal serotonergic axons and, although no biotinylated dextran amine (BDA)-traced corticospinal axons were present within the center of the grafts, the SC transplants significantly increased corticospinal axon numbers immediately rostral to the injury-graft site compared with injury-only controls. Moreover, SC grafted animals demonstrated modest, though significant, improvements in open field locomotion and exhibited less foot position errors (base of support and foot rotation). Whereas these results demonstrate that SC grafts survive, support axon growth, and can improve functional outcome after chronic contusive spinal cord injury, further development of OEG grafting procedures in this model and putative combination strategies with SC grafts need to be further explored to produce substantial improvements in axon growth and function.

show abstract

“…They can become harmful when they synthesise and secrete molecules that increase synaptic overactivity and thus increase the damage already present. They may also alter excitotoxicity, abort apoptosis and encourage the growth of neurite in the injured CNS (Barger et al, 1995;Berezovskaya et al, 1995;Imamura et al, 1990;Lazarov-Spiegler et al, 1996;Prewitt et al, 1997;Rabchevsky and Streit, 1997;Toku et al, 1998). Activated microglias are present in other areas of the CNS and therefore initiate and promote inflammation in different brain regions including the putamen, substantia nigra and cingulated cortex where they are responsible for the generation of lewy bodies (Li et al, 2010;McKeith and Mosimann, 2004;Varani et al, 2010).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Vasoactive Neuropeptides in Autoimmune Diseases

Brenu

Tajouri

Staines³

et al. 2011

Autoimmune Disorders - Current Concepts and Advances From Bedside to Mechanistic Insights

View full text Add to dashboard Cite

Activated Macrophage/Microglial Cells Can Promote the Regeneration of Sensory Axons into the Injured Spinal Cord

Cited by 245 publications

References 54 publications

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Survival, Integration, and Axon Growth Support of Glia Transplanted into the Chronically Contused Spinal Cord

Vasoactive Neuropeptides in Autoimmune Diseases

Contact Info

Product

Resources

About