J Korean Neurosurg Soc.  2017 Jul;60(4):391-396. 10.3340/jkns.2016.1010.018.

Ginkgolide B Modulates BDNF Expression in Acute Ischemic Stroke

Affiliations
  • 1Department of Neurology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
  • 2Department of Neurology, Nanjing General Hospital of Nanjing Command, Nanjing, China.
  • 3Department of Neurology, the First Hospital of Anhui Medical University, Hefei, China. wangkai230001@sina.com

Abstract


OBJECTIVE
To investigate the neuroprotective effects of Ginkgolide B (GB) against ischemic stroke-induced injury in vivo and in vitro, and further explore the possible mechanisms concerned.
METHODS
Transient middle cerebral artery occlusion (tMCAO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells were used to explore the neuroprotective effects of GB. The expression of brain-derived neurotrophic factor (BDNF) was detected via Western blot and qRT-PCR.
RESULTS
GB treatment (4 mg/kg, i. p., bid) significantly reduced neurological deficits, water content, and cerebral infarct volume in tMCAO mice. GB also significantly increased Bcl-2/Bax ratio, reduced the expression of caspase-3, and protected against OGD/R-induced neuronal apoptosis. Meanwhile, GB caused the up-regulation of BDNF protein in vivo and in vitro.
CONCLUSION
Our data suggest that GB might protect the brain against ischemic insult partly via modulating BDNF expression.

Keyword

Stroke; Ginkgolide B; Brain-derived neurotrophic factor; Apoptosis

MeSH Terms

Animals
Apoptosis
Blotting, Western
Brain
Brain-Derived Neurotrophic Factor*
Caspase 3
In Vitro Techniques
Infarction, Middle Cerebral Artery
Mice
Neurons
Neuroprotective Agents
Stroke*
Up-Regulation
Water
Brain-Derived Neurotrophic Factor
Caspase 3
Neuroprotective Agents
Water

Figure

  • Fig. 1 GB attenuated neurological deficits (A) and brain edema (B) 72 hours of reperfusion after 1 hour of tMCAO. All of the mice were suffered from tMCAO. *p<0.05 vs. saline group, mean±standard error of mean, n=10. GB: Ginkgolide B, tMCAO: transient middle cerebral artery occlusion.

  • Fig. 2 GB alleviated infarction 72 hours of reperfusion after 1 hour of tMCAO. All of the mice were suffered from tMCAO. Six consecutive TTC-stained coronal brain slices arranged in cranial to caudal order are shown. The white brain area represents infarcted tissue. *p<0.05, †p<0.01 vs. saline group, mean±standard error of mean, n=6. GB: Ginkgolide B, tMCAO: transient middle cerebral artery occlusion.

  • Fig. 3 GB upregulated the expression of BDNF protein in the per-infarct area forming ipsilateral cerebral cortex. *p<0.05 vs. sham group, †p<0.05 vs. tMCAO group, mean±standard error of mean, n=4. GB: Ginkgolide B, BDNF: brain-derived neurotrophic factor, tMCAO: transient middle cerebral artery occlusion.

  • Fig. 4 GB decreased cell death after OGD/R in N2a cells. Pre-treatment with GB significantly promoted the viability of cells (A), and decreased the release of LDH (B) in a concentration-dependent manner after OGD/R stimulation. *p<0.05, †p<0.01 vs. OGD/R group, mean±standard error of mean of 4 independent experiments. GB: Ginkgolide B, OGD/R: oxygen-glucose deprivation/reoxygenation, LDH: lactate dehydrogenase.

  • Fig. 5 Effects of GB on the protein levels of BDNF, Bcl-2, Bax, pro-Casp 3, and Casp-3 after OGD/R in N2a cells. *p<0.01, †p<0.05 vs. control group, ‡p<0.05 vs. OGD/R group, mean±standard error of mean of 4 independent experiments. GB: Ginkgolide B, BDNF: brain-derived neurotrophic factor, OGD/R: oxygen-glucose deprivation/reoxygenation.


Reference

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