**1. Introduction**

The extracellular matrix (ECM) constitutes a three-dimensional network that surrounds the cells and conform the structure and characteristics to tissues. It has become increasingly evident that once being considered as a bystander between cells, the ECM indeed performs significant functions and involves in controlling various physiological responses in the CNS. The impor‐

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tance of ECM is at three levels: it acts as biological scaffold for the structure of the CNS and controls the diffusion and availability of molecules for biochemical signaling and communica‐ tion and, finally, the various polymers and molecular interactions in the ECM control the biomechanical properties of the central nervous system (CNS) [1, 2]. In addition, regenerative capacity of tissues is also directly related to the ECM. Disorders in mechano-transduction or alterations in the composition of ECM will drive to a loss of the regenerative ability of the tissue and cells [3, 4]. Moreover, a proper immune and toxic response to infections is in accordance with the correct equilibrium in the ECM components [5].

In the nervous system, the ECM are synthesized and secreted by both neurons and glia. In the present chapter, we shall introduce the main key components of the ECM present in the brain and the main implications of these molecules associated to the normal and pathological CNS, including the spinal cord injury and in retina [6, 7]. While axon–glia interaction helps to determine the extent and direction of axon outgrowth, the growth of axons are also directed by factors present in the ECM. The growth enhancing cues such as laminin and fibronectin will encourage the growth and extension of neurites, while the inhibitory cues such as chondroitin sulfate proteoglycans (CSPGs) and semaphorins (Sema) serve as barriers in precise locations to prevent the growth of certain axon pathways into inappropriate areas.
