Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice
(1) Background: Inducing experimental stroke leads to biphasic immune responses, where the early activation of immune functions is followed by severe immunosuppression accompanied by spleen and thymus atrophy. Nicotinamide, a water-soluble B-group vitamin, is a known neuroprotectant against brain is...
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MDPI AG
2023-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2145 |
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| author | Shih-Huang Tai Liang-Chun Chao Sheng-Yang Huang Hsiao-Wen Lin Ai-Hua Lee Yi-Yun Chen E-Jian Lee |
| author_facet | Shih-Huang Tai Liang-Chun Chao Sheng-Yang Huang Hsiao-Wen Lin Ai-Hua Lee Yi-Yun Chen E-Jian Lee |
| author_sort | Shih-Huang Tai |
| collection | DOAJ |
| description | (1) Background: Inducing experimental stroke leads to biphasic immune responses, where the early activation of immune functions is followed by severe immunosuppression accompanied by spleen and thymus atrophy. Nicotinamide, a water-soluble B-group vitamin, is a known neuroprotectant against brain ischemia in animal models. We examined the effect of nicotinamide on the central and peripheral immune response in experimental stroke models. (2) Methods: Nicotinamide (500 mg/kg) or saline was intravenously administered to C57BL/6 mice during reperfusion after transiently occluding the middle cerebral artery or after LPS injection. On day 3, the animals were examined for behavioral performance and were then sacrificed to assess brain infarction, blood–brain barrier (BBB) integrity, and the composition of immune cells in the brain, thymus, spleen, and blood using flow cytometry. (3) Results: Nicotinamide reduced brain infarction and microglia/macrophage activation following MCAo (<i>p</i> < 0.05). Similarly, in LPS-injected mice, microglia/macrophage activation was decreased upon treatment with nicotinamide (<i>p</i> < 0.05), suggesting a direct inhibitory effect of nicotinamide on microglia/macrophage activation. Nicotinamide decreased the infiltration of neutrophils into the brain parenchyma and ameliorated Evans blue leakage (<i>p</i> < 0.05), suggesting that a decreased infiltration of neutrophils could, at least partially, be the result of a more integrated BBB structure following nicotinamide treatment. Our studies also revealed that administering nicotinamide led to retarded B-cell maturation in the spleen and subsequently decreased circulating B cells in the thymus and bloodstream (<i>p</i> < 0.05). (4) Conclusions: Cumulatively, nicotinamide decreased brain inflammation caused by ischemia–reperfusion injury, which was mediated by a direct anti-inflammatory effect of nicotinamide and an indirect protective effect on BBB integrity. Administering nicotinamide following brain ischemia resulted in a decrease in circulating B cells. This warrants attention with respect to future clinical applications. |
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| language | English |
| last_indexed | 2024-03-11T00:06:40Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-9b17eff405d8491d9d52059a9ab27d9e2023-11-19T00:20:02ZengMDPI AGBiomedicines2227-90592023-07-01118214510.3390/biomedicines11082145Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in MiceShih-Huang Tai0Liang-Chun Chao1Sheng-Yang Huang2Hsiao-Wen Lin3Ai-Hua Lee4Yi-Yun Chen5E-Jian Lee6Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan(1) Background: Inducing experimental stroke leads to biphasic immune responses, where the early activation of immune functions is followed by severe immunosuppression accompanied by spleen and thymus atrophy. Nicotinamide, a water-soluble B-group vitamin, is a known neuroprotectant against brain ischemia in animal models. We examined the effect of nicotinamide on the central and peripheral immune response in experimental stroke models. (2) Methods: Nicotinamide (500 mg/kg) or saline was intravenously administered to C57BL/6 mice during reperfusion after transiently occluding the middle cerebral artery or after LPS injection. On day 3, the animals were examined for behavioral performance and were then sacrificed to assess brain infarction, blood–brain barrier (BBB) integrity, and the composition of immune cells in the brain, thymus, spleen, and blood using flow cytometry. (3) Results: Nicotinamide reduced brain infarction and microglia/macrophage activation following MCAo (<i>p</i> < 0.05). Similarly, in LPS-injected mice, microglia/macrophage activation was decreased upon treatment with nicotinamide (<i>p</i> < 0.05), suggesting a direct inhibitory effect of nicotinamide on microglia/macrophage activation. Nicotinamide decreased the infiltration of neutrophils into the brain parenchyma and ameliorated Evans blue leakage (<i>p</i> < 0.05), suggesting that a decreased infiltration of neutrophils could, at least partially, be the result of a more integrated BBB structure following nicotinamide treatment. Our studies also revealed that administering nicotinamide led to retarded B-cell maturation in the spleen and subsequently decreased circulating B cells in the thymus and bloodstream (<i>p</i> < 0.05). (4) Conclusions: Cumulatively, nicotinamide decreased brain inflammation caused by ischemia–reperfusion injury, which was mediated by a direct anti-inflammatory effect of nicotinamide and an indirect protective effect on BBB integrity. Administering nicotinamide following brain ischemia resulted in a decrease in circulating B cells. This warrants attention with respect to future clinical applications.https://www.mdpi.com/2227-9059/11/8/2145nicotinamideneuroprotectionimmunosuppressionanti-inflammatorycirculating B cellsstroke |
| spellingShingle | Shih-Huang Tai Liang-Chun Chao Sheng-Yang Huang Hsiao-Wen Lin Ai-Hua Lee Yi-Yun Chen E-Jian Lee Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice Biomedicines nicotinamide neuroprotection immunosuppression anti-inflammatory circulating B cells stroke |
| title | Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice |
| title_full | Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice |
| title_fullStr | Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice |
| title_full_unstemmed | Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice |
| title_short | Nicotinamide Deteriorates Post-Stroke Immunodepression Following Cerebral Ischemia–Reperfusion Injury in Mice |
| title_sort | nicotinamide deteriorates post stroke immunodepression following cerebral ischemia reperfusion injury in mice |
| topic | nicotinamide neuroprotection immunosuppression anti-inflammatory circulating B cells stroke |
| url | https://www.mdpi.com/2227-9059/11/8/2145 |
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