To test the efficacy of various delivery routes of stem cells to treat cere
bral injury, we investigated the parenchymal distribution of marrow stromal
cells (MSCs) injected into the internal carotid artery (ICA) of the adult
rat after traumatic brain injury (TBI). Bromodeoxyuridine (BrdU)-labeled MS
Cs were injected via the ipsilateral ICA at 24 h after TBI. Using histology
and immunohistochemistry, the distribution of implanted MSCs was analyzed
at 7 days after transplantation. Four groups (n = 4/group) were studied: gr
oup 1, animals transplanted with MSCs cultured with NGF and BDNF at 24 h af
ter TBI; group 2, animals transplanted with MSCs cultured without NGF and B
DNF; group 3, animals injected with a placebo, phosphate buffered saline in
to the ICA at 24 h after TBI; and group 4, rats subjected to TBI only. In g
roups 1 and 2, BrdU-positive cells were localized to the boundary zone of t
he lesion, corpus callosum and cortex of the ipsilateral hemisphere. The nu
mber of BrdU-positive cells was significantly higher in the ipsilateral hem
isphere than in the contralateral hemisphere. More MSCs infused intraarteri
ally engrafted in group 1 (18.9%) than in group 2 (14.4%, p < 0.05). Using
double staining, BrdU-positive cells expressed MAP-2, NeuN, and GFAP in bot
h groups 1 and 2, with this expression being greater in group 1 and the dif
ference between two groups reaching statistical significance in case of MAP
-2. Our data suggest that intraarterial transplantation of MSCs is a viable
route for the intracerebral administration of MSCs for the treatment of TB
I, since MSCs infused intraarterially after TBI survive and migrate into th
e brain. Some implanted MSCs express proteins specific to neurons and astro
cytes. The addition of NGF and BDNF promote migration of MSCs into the brai
n and subsequent expression of neuronal protein MAP-2.