Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats

Abstract

Spinal cord injury (SCI) is a severe condition that affects many people and results in high health care costs. Therefore, it is essential to find new targets for treatment. The fibroblast growth factor receptor 1 (FGFR1) signalling pathway has a history of being explored for SCI treatment. Several groups have examined the effect of high availability of different FGFR1 ligands at the injury site and reported corticospinal tract (CST) regeneration as well as improved motor functions. In this study, we investigated overexpression of the FGFR1 in rat corticospinal neurons in vivo after injury (unilateral pyramidotomy) and in cerebellar granule neurons (CGNs) in vitro. We show that overexpression of FGFR1 using AAV1 intracortical injections did not increase sprouting of the treated corticospinal tract and did not improve dexterity or walking in a rat model of SCI. Furthermore, we show that overexpression of FGFR1 in vitro resulted in decreased neurite outgrowth compared to control. Thus, our results suggest that the FGFR1 is not a suitable therapeutic target after SCI.

Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters

“…The AAV1 serotype is commonly used to transduce the CST via intracortical injections [31][32][33][34][35][36][37][38]. An earlier study that compared seven AAV serotypes (AAV1-AAV6, and AAV8) identified AAV1 and AAV5 as the best and secondbest serotypes to transduce the CST in rats [20].…”

Thermo-sensitive hydrogels combined with decellularised matrix deliver bFGF for the functional recovery of rats after a spinal cord injury

“…Traumatic spinal cord injury (SCI) is a devastating condition characterized by extensive tissue degeneration and severe neurological dysfunction, which affects 250,000 to 500,000 people worldwide1. In detail, 12,000 new cases of SCI occur every year in the USA, and the total number of American individuals living with SCI is estimated at ~259,000.…”

The Function of FGFR1 Signalling in the Spinal Cord: Therapeutic Approaches Using FGFR1 Ligands after Spinal Cord Injury

“…We believe that the focus should shift towards more translatable techniques; however, it is clear that this is not trivial for a ligand that should be delivered very locally in high concentrations over a period of time. We, ourselves, have tried one alternative approach by injecting into the motor cortex adeno associated viruses (AAVs), a delivery method with the advantage of being already used in humans, however, still rather invasive [ 77 ]. Unfortunately, this treatment showed no beneficial effects.…”

“…A different approach of exploring synergism between treatments was taken by ourselves. We hoped to combine the different effects that the various FGF ligands had by overexpressing their common receptor, the FGFR1 [ 77 ]. We did that in a rat model of unilateral pyramidotomy.…”