Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision

Abstract

Neurons in the adult mammalian central nervous system (CNS) have limited capability to regenerate their axons after injury. It is generally accepted that the less capacity of CNS axons to regenerate is partly due to the local environment of the injured CNS axons. Traumatic injury in CNS is often followed by robust glial reaction, the failure of CNS axons to regenerate is partly attributed to the inhibitory surface of the glial scar and extracellular matrix (ECM) produced by oligodendrocytes and astrocytes. The glycosaminoglycan side chains of proteoglycans, such as chondroitin sulfate (CS) are putative components of the ECM contributing to the nonpermissive properties of the injured CNS. Furthermore, a tissue gap formed after traumatic injury would completely block the re-innervation of the CNS axons. In this experiment, the brachium of the superior colliculus was completely transected in a group of 22 adult golden hamsters and 20 μl of 1% Self Assembling Peptide (SAP) and/or 2.5units/ml (final concentration) Chondroitinase ABC were injected into the lesion site. The progression of axonal regeneration and the re-innervations of the superior colliculus were monitored at 4, 6, and 12weeks following the lesion by intravitreal injection of CTB-FITC. We found that SAP nanofiber scaffold used in combination of Chondrointinase ABC could facilitate the retinal fibers to regenerate across the lesion site. The re-innervations of the superior colliculus were observed in the combination group as early as four weeks after the transection while controls showed no reinnervation at any time point. In behavioral study, the adult hamsters showed a functional return of vision in the SAP/Chondroitinase ABC treated cases beginning at 6 weeks post surgery sooner than those treated with either SAP or Chondroitinase ABC alone. Thus, the SAP/Chondroitinase ABC combination is shown to offer an effective new means of creating a more permissive environment for growth after traumatic injury to the CNS, allowing regrowth of axons into the denervated site.