Biology Reference
In-Depth Information
of nerve conduction despite the fact that target reinnervation took place
(
Alto et al., 2009
).
An issue relevant for cell-based therapies, which is not at all addressed at
the preclinical state, is the precise transplantation site. Realistically, trans-
plantation interventions will most likely be performed days to weeks after
injury. Translated to rodents, transplantation delayed for several days makes
the precise identification of the lesion area impossible by just looking at the
cord surface through a microscope. Therefore, the variation of the target site
within the injured spinal cord is significant with the consequence that grafts
are found either in the midst of the cystic lesion at the host-graft border or
even within the mostly uninjured host tissue. Noninvasive high-resolution
imaging techniques need to be introduced in small animals to allow proper
identification and targeting of the defined graft site. Visualization methods
such as high-resolution ultrasound or high-field MRI (
Weber, Vroemen,
Behr, et al., 2006
) are available but not trivial to apply in the preclinical set-
ting. In cell-based clinical trials, ultrasound-guided cell transplantation is be-
coming a standard procedure to delineate the cystic lesion from adjacent
spinal cord (
Lammertse et al., 2012
).
In order not to miss a higher magnitude of structural and in particular
functional effects, repair strategies need to be combined with appropriate
rehabilitation interventions already at the preclinical level. This has been
demonstrated in case of chondroitinase treatment, where the combination
with task-specific rehabilitation (forelimb reaching training) after cervical
SCI significantly augmented behavioral effects observed with the regener-
ative treatment alone (
Garcia-Alias, Barkhuysen, Buckle, et al., 2009
).
Another rationale to introduce rehabilitation already at the preclinical level
is to determine the appropriate timing of regenerative therapies in relation to
the administration of physical therapy activities, which represent standard
care in SCI individuals. Indeed, the parallel combined treatment of
Nogo-A neutralization and locomotor treadmill training in SCI rats yielded
impaired functional outcome (
Maier, Ichiyama, Courtine, et al., 2009
)
suggesting that the timing needs to be adjusted in order to potentiate positive
effects from both approaches.
Almost completely neglected are nonmotor functional deficits such as
bowel and bladder dysfunction impairing quality of life more than any other
SCI sequel particularly in chronic stages (
Anderson, 2004
). Future preclin-
ical studies need to integrate respective parameters (analysis of regrowth of
relevant axon pathways; analysis of relevant functional parameters) to address
patients' unmet medical needs.
