TY - JOUR
T1 - Effects of axonal injury on astrocyte proliferation and morphology in vitro
T2 - Implications for astrogliosis
AU - Guénard, Véronique
AU - Frisch, Gilles
AU - Wood, Patrick M.
N1 - Funding Information:
This work was supported by NIH Grant NS 28059 and NMSS Grant RG 2210-A-2 to P.M.W. and by research funds from The Miami Project to Cure Paralysis. Gilles Frisch was a trainee from Ecole Polytechnique (Palaiseau, France). We thank Drs. Richard P. Bunge and Mary B. Bunge for helpful comments and discussions. The authors are grateful to Lisa A. Gwynn, Ernesto Cuervo, Anna Gomez, LeeAnne Lipson, and Francisco Cruz for expert technical assistance, to Dr. John Klose for performing the statistical analysis, and to Robert Camarina for excellent photographic assistance. The authors especially affirm their undying appreciation to Charlaine Rowlette for her unwavering dedication and consumate expertise in preparing the manuscript. Hybridoma cell lines producing the O4 and O1 antibodies were generous gifts from Dr. Melitta Schachner (Zürich, Switzerland).
PY - 1996/2
Y1 - 1996/2
N2 - Mechanisms inducing gliosis following injury in the central nervous system are poorly understood. We evaluated the effect of axonal injury on astrocyte and Schwann cell proliferation and morphology in vitro. Purified rat dorsal root ganglion neurons grown on monolayers of rat neonatal cortical astrocytes (N-AS(neonatal) cultures) or sciatic nerve-derived Schwann cells (N-SC cultures) were mechanically injured. Noninjured cultures served as controls. Cell proliferation near lesions was monitored by autoradiography 1, 2, 4, and 8 days postinjury. Axonal injury caused a significant transient increase in astrocyte proliferation immediately proximal and distal to the lesion. The lesion did not induce marked changes in the intensity of glial fibrillary acidic protein (GFAP) immunoreactivity. However, processes from GFAP-positive cells usually arranged in random fashion in noninjured cultures were aligned perpendicularly to the cut distal to lesions. Ultrastructural analysis in lesioned N-AS(neonatal) cultures indicated that proximal to the lesion filamented astrocytes were intermingled with axons. Distal to the lesion astrocyte processes formed layers, between which an increased amount of collagen-like material appeared with time postlesion. Axons distal to the lesion degenerated by 2 days, coinciding with the early disappearance of neurofilament immunoreactivity. In noninjured and proximally in injured N-SC cultures, Schwann cells extended processes, engulfing some axons. Distal to the lesion, Schwann cells appeared more rounded and neurites remained until 4 days postinjury. Media conditioned by injured or noninjured N-AS(neonatal) cultures did not affect neuroninduced Schwann cell proliferation. These findings demonstrate that axonal injury and degeneration cause a transient increase in astrocyte proliferation and induce morphological changes in astrocytes consistent with the onset of gliosis.
AB - Mechanisms inducing gliosis following injury in the central nervous system are poorly understood. We evaluated the effect of axonal injury on astrocyte and Schwann cell proliferation and morphology in vitro. Purified rat dorsal root ganglion neurons grown on monolayers of rat neonatal cortical astrocytes (N-AS(neonatal) cultures) or sciatic nerve-derived Schwann cells (N-SC cultures) were mechanically injured. Noninjured cultures served as controls. Cell proliferation near lesions was monitored by autoradiography 1, 2, 4, and 8 days postinjury. Axonal injury caused a significant transient increase in astrocyte proliferation immediately proximal and distal to the lesion. The lesion did not induce marked changes in the intensity of glial fibrillary acidic protein (GFAP) immunoreactivity. However, processes from GFAP-positive cells usually arranged in random fashion in noninjured cultures were aligned perpendicularly to the cut distal to lesions. Ultrastructural analysis in lesioned N-AS(neonatal) cultures indicated that proximal to the lesion filamented astrocytes were intermingled with axons. Distal to the lesion astrocyte processes formed layers, between which an increased amount of collagen-like material appeared with time postlesion. Axons distal to the lesion degenerated by 2 days, coinciding with the early disappearance of neurofilament immunoreactivity. In noninjured and proximally in injured N-SC cultures, Schwann cells extended processes, engulfing some axons. Distal to the lesion, Schwann cells appeared more rounded and neurites remained until 4 days postinjury. Media conditioned by injured or noninjured N-AS(neonatal) cultures did not affect neuroninduced Schwann cell proliferation. These findings demonstrate that axonal injury and degeneration cause a transient increase in astrocyte proliferation and induce morphological changes in astrocytes consistent with the onset of gliosis.
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U2 - 10.1006/exnr.1996.0017
DO - 10.1006/exnr.1996.0017
M3 - Article
C2 - 8635533
AN - SCOPUS:18244419935
VL - 137
SP - 175
EP - 190
JO - Neurodegeneration
JF - Neurodegeneration
SN - 0014-4886
IS - 2
ER -