Lycium Barbarum Polysaccharides Decrease Hyperglycemia-Aggravated Ischemic Brain Injury through Maintaining Mitochondrial Fission and Fusion Balance - PubMed (original) (raw)

. 2017 Jul 7;13(7):901-910.

doi: 10.7150/ijbs.18404. eCollection 2017.

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Lycium Barbarum Polysaccharides Decrease Hyperglycemia-Aggravated Ischemic Brain Injury through Maintaining Mitochondrial Fission and Fusion Balance

Wen-Jing Liu et al. Int J Biol Sci. 2017.

Abstract

Although it has been reported that polysaccharides found in Lycium barbarum possess neuroprotective effects, little is known of their ability to ameliorate hyperglycemia-aggravated ischemia/reperfusion brain injury. In this study, normoglycemic (NG) and hyperglycemic (HG) rats were compared after 30 minutes of middle cerebral artery occlusion (MCAO), followed by 24 or 27 hours of reperfusion, with HG rats pretreated with lyceum barbarum polysaccharides (LBP) or insulin. In each group, the neurological deficit, infarct volume, pathohistology, and expression of proteins, Opa1 and Drp1, were assessed to determine the efficacy of LBP in alleviating hyperglycemia-aggravated ischemia/reperfusion brain injury. Our results show that, compared to the NG group, the HG group had increases in neurological deficits, infarct volume, and evidence of neuronal pyknosis at 24- and/or 72-h of reperfusion (P<0.05) and that pre-treatment with LBP decreased these effects (P<0.05). In addition, immunohistochemistry revealed an increase of Drp1 and a decrease of Opa1 positive neurons in the HG group after 24 and 72 hours of reperfusion when compared to the NG group. LBP treatment prevented the HG-induced alterations in Drp-1 and Opa1 expression. Western blots further confirmed these findings showing that HG caused an increase in phospho-Drp1 and a decrease in Opa1 which were subsequently reversed by LBP addition. These results suggest that hyperglycemia-aggravated ischemic brain damage is associated with an alteration of mitochondrial dynamics and that pre-treatment with LBP ameliorates the hyperglycemia-enhanced ischemic brain damage through maintaining mitochondrial dynamic balance.

Keywords: Lycium barbarum polysaccharides; cerebral ischemia and reperfusion; dynamin-related protein 1; hyperglycemia; mitochondrial fission/fusion; neuroprotection; optic atrophy 1..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1

Figure 1

Body weight and blood glucose changes in NG, HG, LBP, and Insulin groups after STZ administration and after LBP or insulin therapy. A, Summary of body weights; B, Summary of blood glucose levels. *P<0.05, vs. NG group; #P<0.05, vs. HG group, respectively.

Figure 2

Figure 2

Neurological deficits score and T-maze test in sham, NG, HG, LBP and Insulin groups after MCAO and 24- or 72-h reperfusion. A, Summary of the neurological deficits score; B, Summary of the time in T-maze test. *P<0.05,vs. NG group; #P<0.05, vs. HG group, respectively.

Figure 3

Figure 3

Comparison of infarct volumes after 24 hours reperfusion. A, Representative brain sections stained with TTC. Pale areas show infarct volume of the hemisphere in HG and LBP groups; B, Quantitative summary of infarct volumes. *P<0.05, vs. sham group; #P<0.05, vs. HG group, respectively.

Figure 4

Figure 4

Observed histopathology and changes in number of pyknotic cell in NG, HG, LBP and Insulin groups. A, Representative pictograghs of the cortex after 24 and 72 hours reperfusion. Normal histology and neurons are indicated by arrow heads in the sham groups; solid arrows point to pyknotic and swollen neurons after 24 hours reperfusion; glial cells are indicated by empty arrows and compared at 72-h reperfusion. Bar = 100μm. B, Quantitative summary of pyknotic cells; *P<0.05, vs. NG group; #P<0.05, vs. HG group, respectively.

Figure 5

Figure 5

Expression of Opa1 in NG, HG, LBP, and Insulin groups after 24 and 72 hours of reperfusion. A, Representative pictograghs showing immunohistochemistry staining of Opa1. Opa1 positively stained cells appear brown against a blue counterstain (hematoxylin). Yellow arrow heads indicate positively stained cells. Bar = 50 μm. B, Quantitative summary showing the number of Opa1-positive cells; *P<0.05, vs. NG group; #P<0.05 vs. HG group, respectively.

Figure 6

Figure 6

Expression of Drp1 in NG, HG, LBP and Insulin groups after 24 and 72 hours of reperfusion. A, Representative pictograghs showing immunohistochemistry staining of Opa1. Opa1 positively stained cells appear brown against a blue counterstain (hematoxylin). Yellow arrow heads indicate positively stained cells. Bar = 50 μm. B, Quantitative summary showing the number of Drp1-positive cells; *P<0.05, vs. NG group; #P<0.05, vs. HG group, respectively.

Figure 7

Figure 7

Western blotting analysis of Drp1 and Opa1 after 24 and 72 hours of reperfusion. A, Representative Western blot of Opa1, Drp1, and phospho-Drp1; B, Summary of relative values of Opa1; C, Summary of the ratio of phospho-Drp1/Drp1; *P<0.05, vs. NG group; #P<0.05, vs. HG group, respectively.

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