Laminin and heparan sulphate proteoglycan in the lesioned adult mammalian central nervous system and their possible relationship to axonal sprouting

Abstract

Severalin vitro studies indicate that the extracellular matrix (ECM) glycoprotein laminin can promote neurite outgrowth from CNS (central nervous system) neurons. Laminin has been detected immunohistochemically in astrocytes in the embryonic but not the uninjured adult mammalian CNS. In the injured adult CNS, it is found in some reactive astrocytes located near the site of CNS lesions. In the present study, we have attempted to examine the relationship between these laminin⁺ astrocytes and the axonal sprouting that occurs after CNS injuries. This was studied in the intracranially transected adult rat optic nerve which consists of a cranial segment devoid of all retinal ganglion cell axons, and a retinal segment attached to the retina which contains some viable axons that undergo sprouting. Laminin⁺ reactive astrocytes were found in the cranial segment, but not in the retinal segment. In addition, the cut ends of the retinal and cranial segments were capped by an intensely laminin⁺, glial fibrillary acidic protein negative (GFAP) region. Axonal sprouts from the transected retinal ganglion cell axons, identified by anterogradely transported rhodamine isothiocynate (RITC), were confined to laminin⁻, GFAP⁺ regions of the retinal segment. These results suggest that injury-induced axonal sprouting in the adult mammalian CNSin vivo may be promoted by molecules other than laminin, that may be associated with astrocytes. The presence of heparan sulphate proteoglycan HSP G was also examined in the transected optic nerve because the neurite outgrowth promoting factors found in conditioned media derived from several cell typesin vitro have been shown to consist of a complex of laminin and heparan sulphate proteoglycan. No significant changes in heparan sulphate proteoglycan-like immunoreactivity was observed after transection. The presence of laminin and HSPG were also examined in the lesioned adult rat cerebral cortex.