Neural Plasticity / 2018 / Article / Tab 1

Review Article

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Table 1

CNS Inhibitors from myelin, proteoglycans, and ECM. This table summarizes the main inhibitors in the CNS originating from myelin, proteoglycans, and ECM. The table includes some of the inhibitory effects of these molecules in the CNS as well as experimental interventions utilized and trialed to counteract the inhibition. This table is by all means not exhaustive but does highlight several influential studies that have demonstrated inhibition in the CNS and/or ways to counteract it.

MoleculeInhibitory effectInterventions to counteract inhibitionReferences

Myelin-associated inhibitors (MAIs)

Myelin-associated glycoprotein (MAG)Inhibits neurite outgrowthMAG KO mice[52, 53, 7277, 107, 108]
Induces growth cone retractionImmunodepletion of MAG

Nogo-AInhibits neurite outgrowth; induces growth cone collapseAnti-Nogo A antibody[54, 55, 5766, 7880, 8487]
Restriction of synaptic plasticity and learning/memory[91, 93, 94, 100, 101, 107, 108, 116118]

Oligodendrocyte myelin glycoprotein (OMgp)Inhibits neurite outgrowthOMgp KO mice[56, 6771, 84, 107, 108]
Inhibits collateral sprouting

MAI Receptors

Nogo-66 receptor 1 (NgR1)Inhibits neurite outgrowth; induces growth cone collapseNgR1 KO mice[61, 62, 68, 8085, 89, 90, 93, 94]
Restriction of synaptic plasticity and learning/memoryBlocking NgR1 receptor[102, 103, 105, 106, 112114]

Paired immunoglobulin-like receptor B (PirB)Restriction of ocular dominance plasticity; inhibits neuritePirB KO mice[95, 103, 104]
Outgrowth; induces growth cone collapseBlocking PirB receptor

Sphingolipid 1-phopsphate receptor 2 (S1PR2)Inhibits neurite outgrowth; restriction of synaptic plasticityBlocking S1PR2 receptor[88]

ECM and glycoproteins

Chondroitin sulfate proteoglycans (CSPGs—brevican, neurocan, aggrecan, phosphacan, versican)Localized to PNNs; restriction of plasticity through synapticChABC enzyme - removes CS-GAGs of PNNs[10, 1315, 113, 142144, 155]
Stabilization in mature neurons;Novel peptide-mimetic of PTPσ receptor[159163, 168177]
Secreted by reactive astrocytes of glial scar limits remyelinationXyloside treatment (after demyelination)

Link proteins (Crtl1/Hapln1; Bral2/Hapln4)Localized to PNNs; restriction of plasticity through synaptic stabilization in mature neuronsCrtl1 conditional KO mice (neurons)[142, 143, 154]

HyaluronanLocalized to PNNs; restriction of plasticity through synaptic stabilization in mature neuronsInhibitor not yet tested in CNS[142, 143]

Tenascin-R (TN-R)Localized to PNNs; restriction of plasticity through synaptic stabilization in mature neurons;TN-R KO mice[7, 16, 142, 144146, 155, 182, 183, 186, 187]

Tenascin-C (TN-C)Creates neuroanatomical boundaries for growth in development secreted by reactive astrocytes after injuryTN-C KO mice[7, 1719, 155, 179, 180, 183185]
Reexpression of α9β1 receptor

SemaphorinsAxonal guidance/chemorepulsive molecule[188, 190]

Sema 3ALocalized to PNNs; resticition of plasticity through synaptic stabilization in mature neurons; localized to glial scar postinjurySema3A inhibitor (SM-216289)[147, 189, 191193]

Sema 3BLocalized to PNNs; restriction of plasticity through synaptic stabilization in mature neuronsInhibitor not yet tested in CNS[147]

Sema 4DLocalized to myelinating oligodendrocytes in injuryInhibitor not yet tested in CNS[194]