135human mesenchymal stem cells (MSCs) genetically modifi ed to overexpress
BDNF augmented neuroprotection and axonal sprouting [ 198 ]. BDNF is also
correlated with increased axonal growth and sprouting from transplanted cells in
dorsal column lesions [ 195 ]. Further, both Nakajima et al. and Koda et al. found
that in rat contusion models of SCI, treatment with exogenous BDNF was directly
correlated with the survival and rescue of endogenous neurons [ 182 , 199 ] and
oligodendrocytes [ 182 , 200 ].
In the brain, BDNF has been associated with enhancement of mesencephalicdopaminergic neurons and modulation of cognitive processes [ 201 , 202 ]. Several
studies have also demonstrated the importance of BDNF in promoting NPSC dif-
ferentiation in vitro and in vivo after brain injury [ 172 , 203 ]. Despite its wide-
spread benefi ts in the brain, BDNF is not capable of crossing the BBB , rendering
it ineffective when administered intravenously [ 204 , 205 ]. Recently, a technique
was proposed to circumvent this barrier by conjugating BDNF to a molecular
Trojan horse [ 204 ]. The technique was successful in facilitating movement across
the BBB and resulted in decreased infarct volume in a rodent model of stroke
[ 204 ]. Similarly, modifi ed NPSCs overexpressing BDNF have demonstrated
promise as a delivery option, increasing local BDNF mRNA expression in a CCI
model of TBI [ 206 ].
Together, these data suggest that BDNF and NT- 3 are essential molecules forpromoting sprouting and sustained axonal regrowth of both endogenous and trans-
planted cells. As such, various researchers have administered the molecules in com-
bination with promising results. Simultaneous viral-mediated transfection of NT-3
and BDNF showed modest improvement over either growth factor individually in
both in vitro and in vivo murine models of SCI [ 207 ]. Further, intrathecal infusion
of NT-3 and BDNF together for 8 weeks was suffi cient to promote a robust regen-
eration of spinal cord neurons into a nerve graft [ 184 ]. Several other studies found
that direct delivery of BDNF and NT-3 signifi cantly augmented axonal regenera-
tion, myelination, and growth into semipermeable guidance channels in vivo [ 208 –
210 ]. Nonetheless, these molecules are short-lived within the injury site, and
methods of prolonging bioactivity must be implemented in order to consider clini-
cal translation.
7.5.3 Basic Fibroblast Growth Factor- 2
FGF 2 has mitogenic effects on neural progenitor cells within the subventricular
zone (SVZ) and neurotrophic effects on dopaminergic neurons in the postnatal
and adult brain [ 211 – 213 ]. In the non-injured postnatal and adult mouse brain,
intraventricular administration of FGF2 enhances proliferation of neural pro-
genitor cells and increases oligodendrocyte precursor (OPC) generation in the
SVZ [ 211 ]. FGF-2 has, therefore, been considered as a therapeutic treatment in
studies of Parkinson’s disease and other age-related neurodegenerative dis-
eases. In a rodent model of Parkinson’s disease (PD), researchers observed
7 Regenerative Strategies for the Central Nervous System