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. 2021 Jan 18:2021:1587241.
doi: 10.1155/2021/1587241. eCollection 2021.

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Junbin Lin  1 , Chizi Hao  1 , Yu Gong  1 , Ying Zhang  1 , Ying Li  1 , Zhihe Feng  1 , Xiangdong Xu  1 , Hailong Huang  1 , Weijing Liao  1
Affiliations

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Junbin Lin et al. Evid Based Complement Alternat Med. .

Abstract

Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson's correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic presentation of IP and ischemic core.
Figure 2
Figure 2
The chemical structure of TMP.
Figure 3
Figure 3
A brief flowchart of experimental protocol.
Figure 4
Figure 4
Sample collection and measurement of synaptic ultrastructures. (a) 1  mm × 1  mm × 1 mm cerebral parietal cortex tissue samples were collected from IP. (b) Schematic diagram of how to measure the thickness of PSD, width of synaptic cleft, and the length of active zone. (c) Three types of synaptic interface (positively curved, straight, and negatively curved junction). The curvature of straight synapse is 1.00, and a/b is the curvature of the other two types of synapses.
Figure 5
Figure 5
Neurological function by mNSS from 3 d to 28 d after MCAO (mean ± SD, n = 10). ∗ indicates P < 0.05, and ∗∗ indicates P < 0.01 (model vs. TMP).
Figure 6
Figure 6
Identification of SYP by immunohistochemical assay (×400) in IP with time going on 3 d, 7 d, 14 d, and 28 d after MCAO. (a) Representative immunohistochemical images of SYP expression. (b) Quantification of the SYP levels through measuring the IOD values (mean ± SD, n = 6). ∗ indicates P < 0.05, ∗∗ indicates P < 0.01, and ∗∗∗ indicates P < 0.001.
Figure 7
Figure 7
Identification of GAP-43 by immunohistochemical assay (× 400) in IP with time going on 3 d, 7 d, 14 d, and 28 d after MCAO. (a) Representative immunohistochemical images of GAP-43 expression. (b) Quantification of the GAP-43 levels through measuring the IOD values (mean ± SD, n = 6). ∗ indicates P < 0.05, ∗∗ indicates P < 0.01, and ∗∗∗ indicates P < 0.001.
Figure 8
Figure 8
Synaptic ultrastructures in ischemia penumbra of parietal cortex at 28 d after MCAO. (a) Electromicrographs (× 10000) of synaptic ultrastructures (mean ± SD, n = 40 (40 graphs from 4 rats in each group)). (b) Comparison on curvature of synaptic interface. (c) Comparison on thickness of PSD. (d) Comparison on width of synaptic cleft. (e) Comparison on length of active zone. ∗ indicates P < 0.05, ∗∗ indicates P < 0.01, and ∗∗∗ indicates P < 0.001. Scale bar = 200 nm.
Figure 9
Figure 9
Pearson's correlation test. (a) Correlation between mNSS and SYP expression at 28 d after MCAO. (b) Correlation between mNSS and GAP-43 expression at 28 d after MCAO.
Figure 10
Figure 10
Pearson's correlation test between mNSS and synaptic ultrastructures at 28 d after MCAO. (a) Correlation between mNSS and curvature of synaptic interface. (b) Correlation between mNSS and thickness of PSD. (c) Correlation between mNSS and width of synaptic cleft. (d) Correlation between mNSS and length of active zone.
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