Axonal sprouting and laminin appearance after destruction of glial sheaths.

Abstract

Laminin, a large extracellular matrix molecule, is associated with axonal outgrowth during development and regeneration of the nervous system in a variety of animals. In the leech central nervous system, laminin immunoreactivity appears after axon injury in advance of the regenerating axons. Although studies of vertebrate nervous system in culture have implicated glial and Schwann cells as possible sources, the cells that deposit laminin at sites crucial for regeneration in the living animal are not known. We have made a direct test to determine whether, in the central nervous system of the leech, cells other than ensheathing glial cells can produce laminin. Ensheathing glial cells of adult leeches were ablated selectively by intracellular injection of a protease. As a result, leech laminin accumulated within 10 days in regions of the central nervous system where it is not normally found, and undamaged, intact axons began to sprout extensively. In normal leeches laminin immunoreactivity is situated only in the basement membrane that surrounds the central nervous system, whereas after ablation of ensheathing glia it appeared in spaces through which neurons grew. Within days of ablation of the glial cell, small mobile phagocytes, or microglia, accumulated in the spaces formerly occupied by the glial cell. Microglia were concentrated at precisely the sites of new laminin appearance and axon sprouting. These results suggest that in the animal, as in culture, leech laminin promotes sprouting and that microglia may be responsible for its appearance.

Magnitude of [¹¹C]PK11195 Binding Is Related to Severity of Motor Deficits in a Rabbit Model of Cerebral Palsy Induced by Intrauterine Endotoxin Exposure

“…These microglial cells migrate to the cortex, where they are found in their ‘quiescent’ stage during adulthood. During development, activated microglia assume a supportive role in myelinogenesis and axonogenesis by stimulating the synthesis of myelin basic protein and the induction of laminin, an extracellular matrix molecule that enhances neurite outgrowth [12,13]. However, the presence of activated microglia in the white matter tracts during development may also increase the vulnerability of the fetal brain to diverse brain insults.…”

Expression of extracellular matrix components and their receptors in the central nervous system during experimental Toxoplasma gondii and Trypanosoma cruzi infection

“…On the other hand, LN was not detected by our immunohistochemical assays in these inflammatory infiltrates, suggesting a more effective involvement of FN in the genesis of CNS inflammatory lesions during T. gondii infection. Concerning the origin of this FN, it is possible that nervous or mononuclear cells present in the inflammatory infiltrates could release ECM molecules in nervous tissue (25)(26)(27). Indeed, some studies have demonstrated that motor neurons, glial cells and astrocytes are able to secrete ECM molecules such as FN and LN when neuronal-glial interaction occurs and during the astrocyte proliferative response following injury (25,26).…”

Reduced axon sprouting after treatment that diminishes microglia accumulation at lesions in the leech CNS

“…Microglia stimulation is generally considered to involve activation by 1) molecules released directly by a lesion; or 2) a signal propagating from the site of injury via other cells, such as a calcium wave carried by glia. Such activated microglia, when accumulated at a lesion, would be expected in mammals to release neurotrophins such as brain-derived neurotrophic factor (BDNF), neurotrophic factor (NTF), and NT3 (Batchelor et al, 1999) and in leeches perhaps laminin (Masuda-Nakagawa et al, 1993), all of which have been shown to enhance axon growth and neuron survival. In addition, in the rat it has been shown that damage to the lens causes macrophages to release proteins that promote regeneration of retinal ganglion cell axons (Leon et al, 2000;Yin et al, 2003Yin et al, , 2006.…”