http://www.sciencedirect.com/science/article/pii/S0166432817303042
Highlights
- •
- dl-NBP promoted the behavioral performance after cerebral ischemia in rats.
- •
- dl-NBP improved the behavioral recovery possibly by increasing neurogenesis, axonal regeneration and synapse formation.
- •
- The axonal regeneration promoted by dl-NBP may be mediated through the Nogo-A/NgR and RhoA/ROCK pathway.
Abstract
Backgrounds and aims
Racemic l-3-n-butylphthalide (dl-NBP),
is able to achieve a functional recovery in animal models of cerebral
ischemia, vascular dementia, and Alzheimer’s disease. In this study, we
investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia.
Methods
Focal
cerebral ischemia in rats was produced by intracerebral injection of
endothelin-1. Starting from postoperative day 7, the experimental rats
were administered 70 mg/kg dl-NBP by oral
gavage for two weeks. Biotinylated dextran amine (BDA) was injected
into the contralateral sensorimotor cortex on day 14 after ischemia to
trace the sprouting of corticospinal tract (CST) fibers into the
denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R,
Rho-A, and ROCK in the perilesional cortex, the expressions of BDA,
PSD-95, and vGlut1 in the denervated spinal cord,
5-bromo-20-deoxyuridine (BrdU)/DCX-positive cells in the subventricular
zone (SVZ) of the injured hemisphere were detected by
immunofluorescence. The rats’ behavioral abilities were measured on
postoperative days 30–32 in the beam-walking, cylinder and sticky label
tests.
Results
dl-NBP
treatment significantly increased the number and length of crossing CST
fibers, enhanced significantly the expression levels of
synapse-associated proteins including PSD95 and VGlut-1 in the
denervated cervical spinal cord, elevated the number of BrdU+/DCX+ cells
in SVZ, and reduced markedly those of Rho-A+, ROCK+, Nogo-A+ and
Nogo-R+ cells in perilesional cortex. In addition, dl-NBP improved the behavioral performance of the ischemic rats.
Conclusion
dl-NBP enhanced the behavioral recovery after cerebral ischemia in rats, possibly by increasing axonal growth and neurogenesis.
Keywords
- Axonal growth;
- dl-NBP;
- Neurogenesis;
- Stroke
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