Biology Reference
In-Depth Information
1.1. Stimulated macrophages
One hypothesis explaining the poor regenerative capacity of the injured
CNS is based on the differential immune response in the injured peripheral
versus the CNS. Macrophages in the peripheral nervous system are consid-
ered as key players to remove debris after injury and secrete appropriate
growth factors to pave the road for successful axon regrowth. This aspect
is missing in the immune-privileged CNS, thus contributing to poor intrin-
sic tissue repair. The group around Michal Schwartz demonstrated that the
transfer of macrophages incubated with pieces of peripheral nerve prior to
transplantation promotes limited repair of injured optical nerve (
Lazarov-
Spiegler, Solomon, Zeev-Brann, et al., 1996
).
This approach was transferred to the completely transected rat spinal cord
(T8/9 level) (
Rapalino et al., 1998
). Animals received homologous blood-
derived macrophage grafts (after prior incubation with peripheral nerve) at
and caudal to the lesion site. Animals were assessed up to 19 weeks post
injury. Subgroups were generated based on the arbitrary assumption that
BBB scores (locomotor rating scale for open field testing in rats from 0 to
21;
Basso, Beattie, & Bresnahan, 1995
) up to 5 were not considered as re-
covery but rather local reflex activity. Animals receiving macrophage grafts
with a BBB score
>
5 reached an average score of 7.1, whereas animals from
the same group with a BBB score
5 averaged at 3.4. Control animals re-
ceiving (1) medium, (2) aFGF, or (3) fibrin glue injection had average BBB
scores of 1.1. Motor-evoked potential (MEP) responses recovered only in 2/
12 treated animals, not in control animals. Supraspinal input rather than
mechanisms of the local spinal circuitry was considered to be responsible
for the observed locomotor recovery since retransection abolished the ob-
served MEP recovery. Precise structural correlates (e.g., target rein-
nervation, remyelination), which could have accounted for the observed
functional recovery, were not shown. The fate of grafted macrophages in
terms of survival and migration behavior was not investigated. One
follow-up study supported these findings demonstrating functional recovery
in rat contusion SCI with grafted macrophages, which were stimulated with
dermis instead of peripheral nerve (
Bomstein et al., 2003
). The phenotype of
macrophages after coincubation with dermis was analyzed (expression of
CD86, CD54, MHC class II, CD80; secretion of soluble factors), however,
not compared with previously described preparations of peripheral nerve-
stimulatedmacrophages. Macrophages were grafted between 4 and 9 days post
contusion into the “caudal border of the lesion” (
Bomstein et al., 2003
).
