J Cerebrovasc Endovasc Neurosurg.  2018 Sep;20(3):159-167. 10.7461/jcen.2018.20.3.159.

Diverse Ischemic Postconditioning Protocols Affect the Infarction Size in Focal Ischemic Stroke

• Lee JS
• Song DJ
• Hong JH
• Kim TS
• Joo SP

• KMID: 2422767
• DOI: http://doi.org/10.7461/jcen.2018.20.3.159

Abstract

OBJECTIVE
Ischemic postconditioning (IPostC), consisted of transient brain ischemia/reperfusion cycles, is considered to have neuroprotective effect. However, there is no best single protocol of IPostC, because varied factors like species tested and characteristics of the tissue may affect the efficacy of IPostC. Thus, we investgated whether different protocols of IPostC affect neuroprotective effects in experimental animal models.
MATERIALS AND METHODS
Through occlusion of middle cerebral artery (MCA) with intraluminal suture, stroke was induced in a transient focal ischemia model in mice. We conducted IPostC via brief and repeated MCA occlusion, 2 minutes after reperfusion, followed by different ischemia and reperfusion protocols. After procedure, functional neurological score and histological examination were evaluated.
RESULTS
IPostC with different protocols resulted in diverse effects. Among them, a protocol that consists of 3 cycle of IPostC significantly reduced the infarction size 3 days after stroke.
CONCLUSION
IPostC was confirmed to reduce infarction size. The effects of IPostC are definitely affected by differences in the protocol used, including the number of cycles, the duration of individual ischemia/reperfusion episode and the entire duration of the IPostC stimuli.

Keyword

Ischemia; Ischemic postconditioning; Infarction; Protocol

MeSH Terms

Animals
Brain
Infarction*
Ischemia
Ischemic Postconditioning*
Mice
Middle Cerebral Artery
Models, Animal
Neuroprotective Agents
Reperfusion
Stroke*
Sutures
Neuroprotective Agents

Figure

• 

  Fig. 1 Experimental protocols. Focal ischemia was induced by of temporary occlusion of middle cerebral artery for 60 minutes. This study compared the protective effects of IPostC with 1, 3, 5, and 10 cyclese of 15 seconds occlusion/30 seconds reperfusion initiated 2 minutes post-reperfusion. Group C is the ischemic control, without IPostC. IPostC was initiated 2 minutes after reperfusion, and consisted of a differing number of cycles of 15 seconds occlusion/30 seconds reperfusion. N = 10 mice/group. IPostC = ischemic postconditioning.

• 

  Fig. 2 TTC staining and infarction volume. (A) TTC staining from representative examples of infarctions are shown in the top panel. (B) The bar graph shows the average infarct volume in each group. IPostC with 3 cycles provided the strongest protection, while IPostC with 1, 5, or 10 cycles did not sufficiently reduce the infarction size. Data are showed by the mean ± scanning electron microscope. N = 10 mice/group. TTC = triphenyltetrazolium chloride; IPostC = ischemic postconditioning. *p < 0.05; †p < 0.01 compared to control group.

• 

  Fig. 3 Experimental protocols, TTC staining and infarction volume. (A) Focal ischemia was induced by 60 minutes of transient middle cerebral artery occlusion. Group I is the ischemic control without IPostC (n = 10). Group II was initiated 2 minutes after reperfusion, 3 cycles of 15 seconds occlusion/30 seconds reperfusion were performed (n = 10). Group III was initiated 2 minutes after reperfusion, 3 cycles of 30 seconds occlusion/15 seconds reperfusion (the reversal of the pattern used in group II) were performed (n = 10). (B) TTC staining from representative examples of infarctions are shown. (C) Graph shows the average volume of infarction in each group. IPostC, which did 3 cycles of 15 seconds occlusion/30 seconds reperfusion provided the strongest protection compared to 3 cycles of 30 seconds occlusion/15 seconds reperfusion. Data are presented as the mean ± scanning electron microscope. N = 10 mice/group. TTC = triphenyltetrazolium chloride; IPostC = ischemic postconditioning. *p < 0.05; †p < 0.01 compared to control group.

• 

  Fig. 4 The long-term effects of IPostC. (A) Silver staining from representative examples of infarctions are shown 14 days after stroke. (B) Graph shows the average infarct volume between the two groups. (C) The histogram shows the average FNS. severe scores mean greater impairment. Both 1 day and 3 day after reperfusion, FNS of all IPostC groups was improved significantly, compared with the FNS of control group FNS. Con = control; IPost = ischemic postconditioning; FNS = focal neurological scores; IPostC = ischemic postconditioning. *p < 0.05. †p < 0.01. ‡p < 0.001.

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