Figure 9.

Proposed model of BDNF role in NDO emergence and maintenance. Our main experimental findings show that preventing the increased spinal BDNF, which occurs after cord injury, induces early NDO, as a consequence of premature sprouting of sensory afferents, This suggests that BDNF may exert a protective role on bladder function after SCI. Thus, chronic BDNF administration at the spinal cord level, also initiated immediately after spinal lesion, resulted in an amelioration of bladder function of SCI, compared with animals receiving vehicle. In this case, axonal growth was less prominent. We propose that SCI induces sprouting of sensory afferents, possibly as a consequence of upregulation of trophic factors, such as NGF. These afferents establish new synaptic connections at the spinal cord, which lead to an abnormal micturition reflex, totally located at the lumbosacral spinal cord. At the same time, spinal BDFN increases in an attempt to repress axonal sprouting at the spinal cord. Once the new connections are established, BDNF acts as a neurotransmitter, released upon stimulation of bladder afferents, and potentiates bladder dysfunction. Accordingly, BDNF sequestration in rats with established NDO blocked bladder reflex contractions.