Effects of axonal injury on astrocyte proliferation and morphology in vitro: implications for astrogliosis.
Mechanisms inducing gliosis following injury in the central nervous sy stem 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-ASneonatal cultures) or sciatic nerve-derived Schwann cells (N-SC cultures) were mechanically injured. Non-injured 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-ASneonatal cultures indicated that proximal to the lesion filament-filled 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 non-injured N-ASneonatal cultures did not affect neuron-induced 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.
Guenard
V
V
Department of Neurological Surgery, University of Miami School of Medicine, Florida 33143, USA.
Frisch
G
G
Wood
P M
PM
D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology*; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000473:pathology