L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats.

Abstract

AIMS:

This study investigated whether anticerebral ischemia new drug, l-3-n-butylphthalide (l-NBP), improved behavioral recovery and enhanced hippocampal neurogenesis after cerebral ischemia in rats.

METHODS AND RESULTS:

The middle cerebral artery of rats was blocked for 2 h. The daily oral administrations of 30 mg/kg l-NBP or vehicle were begun from the second day until the rats were sacrificed. L-NBP treatment markedly increased 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the hippocampal dentate gyrus (DG) of injured hemisphere on day 28 after ischemia. The amount of newborn cells and newly mature neurons was also increased. The expressions of growth-associated protein-43 and synaptophysin were significantly elevated in l-NBP-treated rats. However, l-NBP markedly reduced the percentage of BrdU(+) /GFAP(+) cells. Additionally, the levels of catalytical subunit of protein kinase A (PKA), protein kinase B (Akt), and cAMP response element-binding protein (CREB) were significantly increased, and the activation of the signal transducer and activation of transcription 3 (STAT3) and the expressions of cleaved caspase-3 and Bax were obviously inhibited by l-NBP. Consequently, l-NBP attenuated the behavioral dysfunction.

CONCLUSIONS:

It first demonstrates that l-NBP may improve the behavioral outcome of cerebral ischemia by promoting neurogenesis and neuroplasticity. Activation of CREB and Akt and inhibition of STAT3 signaling might be involved in.

• Authors: Li-Chao Yang, Jiang Li, Shao-Feng Xu, Jie Cai, Hui Lei, Dong-Mei Liu, Man Zhang, Xian-Fang Rong, Dan-Dan Cui, Ling Wang, Ying Peng, Xiao-Liang Wang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 21 Issue 9 Pg. 733-41 (Sep 2015) ISSN: 1755-5949 [Electronic] England
• PMID: 26215907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Benzofurans
• Cyclic AMP Response Element-Binding Protein
• Neuroprotective Agents
• STAT3 Transcription Factor
• Stat3 protein, rat
• 3-n-butylphthalide
• Proto-Oncogene Proteins c-akt

Topics

• Administration, Oral
• Animals
• Apoptosis (drug effects, physiology)
• Benzofurans (pharmacology)
• Brain Ischemia (drug therapy, pathology, physiopathology)
• Cell Survival (drug effects, physiology)
• Cognition (drug effects, physiology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Disease Models, Animal
• Hippocampus (drug effects, pathology, physiopathology)
• Infarction, Middle Cerebral Artery
• Male
• Neural Stem Cells (drug effects, pathology, physiology)
• Neurogenesis (drug effects, physiology)
• Neuronal Plasticity (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• STAT3 Transcription Factor (metabolism)
• Synapses (drug effects, physiology)