http://thejns.org/doi/abs/10.3171/2012.11.JNS12753
Abstract
Object
This
study was designed to investigate how transplantation into injured
brain of human bone marrow stromal cells (hMSCs) impregnated in collagen
scaffolds affects axonal sprouting in the spinal cord after traumatic
brain injury (TBI) in rats. Also investigated was the relationship of
axonal sprouting to sensorimotor functional recovery after treatment.
Methods
Adult
male Wistar rats (n = 24) underwent a controlled cortical impact injury
and were divided into three equal groups (8 rats/group). The two
treatment groups received either hMSCs (3 × 106) alone or hMSC (3 × 106)–impregnated
collagen scaffolds transplanted into the lesion cavity. In the control
group, saline was injected into the lesion cavity. All treatments were
performed 7 days after TBI. On Day 21 after TBI, a 10% solution of
biotinylated dextran amine (10,000 MW) was stereotactically injected
into the contralateral motor cortex to label the corticospinal tract
(CST) originating from this area. Sensorimotor function was tested using
the modified neurological severity score (mNSS) and foot-fault tests
performed on Days 1, 7, 14, 21, 28, and 35 after TBI. Spatial learning
was tested with Morris water maze test on Days 31–35 after TBI. All rats
were sacrificed on Day 35 after TBI, and brain and spinal cord
(cervical and lumbar) sections were stained immunohistochemically for
histological analysis.
Results
Few
biotinylated dextran amine–labeled CST fibers crossing over the midline
were found in the contralateral spinal cord transverse sections at both
cervical and lumbar levels in saline-treated (control) rats. However,
hMSC-alone treatment significantly increased axonal sprouting from the
intact CST into the denervated side of the gray matter of both cervical
and lumbar levels of the spinal cord (p < 0.05). Also, this axonal
sprouting was significantly more in the scaffold+hMSC group compared
with the hMSC-alone group (p < 0.05). Sensorimotor functional
analysis showed significant improvement of mNSS (p < 0.05) and
foot-fault tests (p < 0.05) in hMSC-alone and scaffold+hMSC-treated
rats compared with controls (p < 0.05). Functional improvement,
however, was significantly greater in the scaffold+hMSC group compared
with the hMSC-alone group (p < 0.05). Morris water maze testing also
showed significant improvement in spatial learning in scaffold+hMSC and
hMSC-alone groups compared with the control group (p < 0.05), with
rats in the scaffold+hMSC group performing significantly better than
those in the hMSC-alone group (p < 0.05). Pearson correlation data
showed significant correlation between the number of crossing CST fibers
detected and sensorimotor recovery (p < 0.05).
Conclusions
Axonal
plasticity plays an important role in neurorestoration after TBI.
Transplanting hMSCs with scaffolds enhances the effect of hMSCs on
axonal sprouting of CST fibers from the contralateral intact cortex into
the denervated side of spinal cord after TBI. This enhanced axonal
regeneration may at least partially contribute to the therapeutic
benefits of treating TBI with hMSCs.
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