Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters

Abstract

A tissue gap caused by deep transections of the optic tract (OT) in the midbrain can completely block the re-innervation of the superior colliculus (SC) by the retina. We find that a self-assembling peptide (SAP) nanofiber scaffold used in combination of ciliary neurotrophic factor (CNTF) can facilitate the reconstruction of a tissue substrate that supports regeneration across the tissue disruption and CNTF promoted growth of axons across the injury site. Brain wounds were inflicted in anesthetized adult Syrian hamsters. The scalp and skull were opened surgically and the OT at the brachium of the SC was completely severed with a deep knife wound, extending 1-2 mm below the surface from the midline to a point beyond the lateral margin of SC. In a group of young adult hamsters (8 wk) following the transection of the optic tract at the brachium of the SC the animals were treated by injection, into the site of injury 100 ul of 1% SAP RAD16-I. These experimental animals received 5 intravitreal injections of CNTF once every five days. For controls 100 µl of saline was injected in place of CNTF. Axons grew across the lesion site in the SAP & CNTF treated cases. Histological results revealed that only in the animals treated with SAP & CNTF, the tissue appears to have reconnected across the lesion 6 weeks post surgery. In behavioral studies the adult hamsters showed a functional return of vision in the SAP/CNTF treated cases beginning at 6 weeks post surgery. Thus, the SAP CNTF combination is shown to offer an effective new means of creating a permissive environment for axonal growth while CNTF promotes growth of axons across this environment in tissue disruptions caused by traumatic injury to the CNS, allowing regrowth of axons into the SC and functional return of vision.