Picroside II Inhibits Neuronal Apoptosis and Improves the Morphology and Structure of Brain Tissue following Cerebral Ischemic Injury in Rats

Tingting Wang; Li Zhao; Yunliang Guo; Meizeng Zhang; Haitao Pei

doi:10.1371/journal.pone.0124099

Picroside II Inhibits Neuronal Apoptosis and Improves the Morphology and Structure of Brain Tissue following Cerebral Ischemic Injury in Rats

PLoS One. 2015 Apr 30;10(4):e0124099. doi: 10.1371/journal.pone.0124099. eCollection 2015.

Authors

Tingting Wang¹, Li Zhao¹, Yunliang Guo¹, Meizeng Zhang¹, Haitao Pei¹

Affiliation

¹ Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders; Taishan Scholars Construction Project Excellent Innovative Team of Shandong Province, Qingdao, 266003, P. R. China.

Abstract

This paper aimed to explore the protective effects of picroside II against the neuronal apoptosis and changes in morphology and structure that follow cerebral ischemic injury in rats. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO) in 60 Wistar rats, and intraperitoneal injections of picroside II (20 mg/kg) were administered. The neurobehavioral functions were evaluated with the modified neurological severity score (mNSS) test. The cerebral infarct volumes were measured with tetrazolium chloride (TTC) staining. The morphology and ultrastructure of the cortical brain tissues were observed with hematoxylin-eosin staining and transmission electron microscopy, respectively. The apoptotic cells were counted with terminal deoxynucleotidyl transferase dUTP nick-end labeling and flow cytometry, and pERK1/2 expression was determined by immunohistochemical assay and Western blot. The results indicated that neurological behavioral malfunctions and cerebral infarcts were present in the MCAO rats. In the model group, the damage to the structures of the neurons and the blood brain barrier (BBB) in the cortex was more severe, and the numbers of apoptotic cells, the early apoptotic ratio (EAR) and pERK1/2 expression were significantly increased in this group compared to the control group (P<0.05). In the treatment group, the neurological behavioral function and the morphology and ultrastructure of the neurons and the BBB were improved including the number of Mi increased and relative area of condensed chromosome and basement (BM) thickness descreased, and the cerebral infarct volume, the number of apoptotic cells, the EAR and pERK1/2 expression were significantly decreased compared to the model group (P<0.05). These results suggest that picroside II reduced apoptosis and improved the morphology and ultrastructure of the neurons and the BBB and that these effects resulted in the recovery of the neurobehavioral function of rats with cerebral ischemia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Blotting, Western
Brain / cytology*
Brain Ischemia / drug therapy*
Brain Ischemia / metabolism
Cinnamates / therapeutic use*
Flow Cytometry
Immunohistochemistry
In Situ Nick-End Labeling
Iridoid Glucosides / therapeutic use*
Male
Microscopy, Electron, Transmission
Neurons / cytology
Neurons / drug effects*
Rats
Rats, Wistar

Substances

Cinnamates
Iridoid Glucosides
picroside II

Grants and funding

This experiment was supported by grant-in-aids for the Natural Science Fund of China (81274116, 81041092). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.