Neurotrophic factors for spinal cord repair: Which, where, how and when to apply, and for what period of time?

The role of growth factors in nerve regeneration

“…This state is supported by the results of studies conducted with the combinations of GDNF and neuropoeitic cytokines, which argue that they either increase each other's present effects or show a synergistic effect (9,22). It has been reported that in the differentiation of embryonic motor neurons, neurotrophic factors of each of the three families improve neurite outgrowth, even if in different degrees, and that different combinations show synergistic effect (23).…”

“…It has been reported that neurotrophic factors provide neural survival following damage and that there is a direct association between exogenous neurotrophic factor application and axonal regeneration (22,49). In the evaluation of peripheral nerve regeneration, total number of axons in the distal part of nerve and functional tests are used (50)(51)(52).…”

Neurotrophic Factors Used to Treat Spinal Cord Injury

“…Previously, we reported preliminary data using bi-cistronic AAV vectors (serotype 2.1) to introduce neurotrophic factors (AAV-CNTF mCherry ) into cortical neurons in adult rat sensorimotor cortex, with the eventual aim of combining this approach with cellular bridging grafts in the injured spinal cord (Harvey et al, 2015). We are in the process of carrying out such combinatorial studies using MPCs to stabilize the lesion site to improve the peri-lesion terrain through which CST axons can regenerate.…”

“…Although functional improvements are not always observed, a majority of studies have found that most neurotrophic/growth factors can enhance locomotor recovery to some extent, especially when assessing hindlimb function after thoracic SCI. Note that it is the norm to cite and compare mean group values when reporting functional or histological outcomes, but correlative analysis of morphology/ connectivity with sensorimotor performance at the individual animal level is rarely undertaken (Harvey et al, 2015). Of course, delivery of factors into the lesion area may affect numerous axons and/or cell populations in different ways, with complex and not always predictable outcomes.…”

“…As discussed in detail elsewhere (Harvey et al, 2015), it is essential to determine where best to apply such factors and how to administer them. Growth factors can be delivered: (i) in and/or immediately around the spinal cord lesion itself, (ii) to location(s) containing the neurons whose axons are affected by injury, and/or (iii) via intrathecal or systemic application.…”