Adeno-associated virus-mediated L1 expression promotes functional recovery after spinal cord injury

• DOI: 10.1093/brain/awm049
• Publication Date: 2007-04-16T15:48:16Z
• Authors: Jian Chen; Junfang Wu; Ivayla Apostolova; Malgorzata Skup; Andrey Irintchev; Sebastian Kügler; Melitta Schachner
• Keywords: Glial scar; Corticospinal tract; Chondroitin sulfate proteoglycan; Neurite; Astrogliosis

Paucity of permissive molecules and abundance inhibitory in the injured spinal cord adult mammals prevent axons from successful regeneration and, thus, contribute to failure functional recovery. Using an adeno-associated viral (AAV) vector, we expressed regeneration-promoting cell adhesion molecule L1 both neurons glia lesioned mice. Exogenous L1, detectable already 1 week after thoracic compression immediate vector injection, was at high levels up 5 weeks, longest time-period studied. Dissemination L1-transduced cells throughout wide, spanning over more than 10 mm rostral caudal lesion scar. not fibronectin-positive core. overexpression led improved stepping abilities muscle coordination during ground locomotion a 5-week observation period. Superior improvement associated with enhanced reinnervation lumbar by 5-HT axons. Corticospinal tract did regrow beyond scar but extended distally into closer proximity injury site AAV-L1-treated compared control The expression neurite outgrowth-inhibitory chondroitin sulphate proteoglycan NG2 decreased cords, along reduction reactive astroglial marker GFAP. In vitro experiments confirmed that inhibits astrocyte proliferation, migration, process extension GFAP expression. Analyses intracellular signalling indicated exogenous activates diverse cascades glia. Thus, AAV-mediated appears be potent means favourably modify local environment promote regeneration. Our study demonstrates clinically feasible approach promising potential.