Korean J Physiol Pharmacol.  2020 Mar;24(2):165-171. 10.4196/kjpp.2020.24.2.165.

Changes in plasma lipoxin A4, resolvins and CD59 levels after ischemic and traumatic brain injuries in rats

• Jung JS
• Kho AR
• Lee SH
• Choi BY
• Kang SH
• Koh JY
• Suh SW
• Song DK

• KMID: 2471038
• DOI: http://doi.org/10.4196/kjpp.2020.24.2.165

Abstract

Ischemic and traumatic brain injuries are the major acute central nervous system disorders that need to be adequately diagnosed and treated. To find biomarkers for these acute brain injuries, plasma levels of some specialized pro-resolving mediators (SPMs, i.e., lipoxin A4 [LXA4], resolvin [Rv] E1, RvE2, RvD1 and RvD2), CD59 and interleukin (IL)-6 were measured at 0, 6, 24, 72, and 168 h after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. Plasma LXA4 levels tended to increase at 24 and 72 h after GCI. Plasma RvE1, RvE2, RvD1, and RvD2 levels showed a biphasic response to GCI; a significant decrease at 6 h with a return to the levels of the sham group at 24 h, and again a decrease at 72 h. Plasma CD59 levels increased at 6 and 24 h post-GCI, and returned to basal levels at 72 h post-GCI. For TBI, plasma LXA4 levels tended to decrease, while RvE1, RvE2, RvD1, and RvD2 showed barely significant changes. Plasma IL-6 levels were significantly increased after GCI and TBI, but with different time courses. These results show that plasma LXA4, RvE1, RvE2, RvD1, RvD2, and CD59 levels display differential responses to GCI and TBI, and need to be evaluated for their usefulness as biomarkers.

Keyword

CD59; Ischemic brain injury; Lipoxin A4; Resolvins; Traumatic brain injury

MeSH Terms

Animals
Biomarkers
Brain Injuries*
Central Nervous System Diseases
Interleukin-6
Interleukins
Lipoxins*
Plasma*
Rats*
Biomarkers
Interleukin-6
Interleukins
Lipoxins

Figure

• 

  Fig. 1 Changes in the plasma lipoxin A4 (LXA4) levels after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. GCI (A) and TBI (B) in rats were induced as described in Methods. After anesthesia, blood (1.5 ml) was collected from retro-orbital venous plexus at 6, 24, 72, and 168 h after the respective injury. The number of animals was 5 for sham and experimental groups. Plasma LXA4 levels were measured with ELISA. For normal plasma LXA4 levels, blood was collected from three naïve animals. Mean ± SEM is shown.

• 

  Fig. 2 Changes in the plasma resolvin (Rv) E1, RvE2, RvD1, and RvD2 levels after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. GCI and TBI in rats were induced as described in Methods. After anesthesia, blood (1.5 ml) was collected from retroorbital venous plexus at 6, 24, 72, and 168 h after the respective injury. The number of animals was 5 for sham and experimental groups. Plasma RvD1 (A, B), RvD2 (C, D), RvE1 (E, F) and RvE2 (G, H) levels were measured with ELISA. For normal plasma resolvins levels, blood was collected from three naïve animals. Mean ± SEM is shown. **p < 0.01, ***p < 0.001, ****p < 0.0001; compared to the sham group.

• 

  Fig. 3 Changes in the plasma CD59 levels after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. GCI (A) and TBI (B) in rats were induced as described in Methods. After anesthesia, blood (1.5 ml) was collected from retro-orbital venous plexus at 6, 24, 72, and 168 h after the respective injury. The number of animals was 5 for sham and experimental groups. Plasma CD59 levels were measured with ELISA. For normal plasma CD59 levels, blood was collected from three naïve animals. Mean ± SEM is shown. **p < 0.01, ***p < 0.001; compared to the sham group.

• 

  Fig. 4 Changes in the plasma interleukin (IL)-6 levels after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. TBI (B) in rats were induced as described in Methods. After anesthesia, blood (1.5 ml) was collected from retro-orbital venous plexus at 6, 24, 72, and 168 h after the respective injury. The number of animals was 5 for sham and experimental groups. Plasma IL-6 levels were measured with ELISA. For normal plasma IL-6 levels, blood was collected from three naïve animals. Mean ± SEM is shown. **p < 0.01, ***p < 0.001, ****p < 0.0001; compared to the sham group.

• 

  Fig. 5 Neuronal death and glial activation after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. (A) Representative images show Fluoro Jade-B (FJB) staining to detect degenerating neurons. The number of degenerating neurons were significantly increased in the hippocampal CA1 at 3 days after GCI or TBI. Scale bar, 20 µm. (B, C) Representative immunofluorescence images show the expression of ionized calcium binding adaptor molecule-1 (Iba-1, green signal) or glial fibrillary acidic protein (GFAP, red signal) in the hippocampal CA1 at 7 days after GCI or TBI. Microglial (B) and astroglial (C) activation were increased in the hippocampus after GCI or TBI compared with sham-operated rats. Scale bar, 20 µm.

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