Nicotinamide reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats

Tsung Ying Chen, Yu Hsiang Kuan, Hung Yi Chen, Ming Yang Lee, E-Jian Lee

Research output: Contribution to journalArticle

Abstract

We have previously shown that nicotinamide protects against energy depletion and decreases infarction in a rat model of cerebral ischemia [1, 2]. It is known that postischemic cell-mediated neuroinflammation exaggerates the initial brain insult caused by ischemia. Herein, we explored whether nicotinamide mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Nicotinamide (NICO, 500 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, NICO-treated animals resulted in significantly decreased macrophages (4.57(x105)±3.00 vs. 2.83(x105)±1.42) and T lymphocytes (0.74(x105)±0.57 vs. 0.28(x105)±1.42) in the bloodstream (P>0.05). Treatment with NICO also significantly decreased the cellular inflammatory response in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 55% (P<0.01) and 66% (P<0.01), respectively. In addition, NICO significantly decreased the population composition of T lymphocyte (CD3-positive/CD45-positive; P<0.001) by 39%. This NICO-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction by 34% (P<0.05) and improved surviving neurons in penumbral cortex and caudoputamen by 112% (P<0.005) and 250% (P<0.001), respectively. Thus, intravenous administration of NICO upon reperfusion effectively decreased the emigration of circulatory neutrophils, T-lymphocytes and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates nicotinamide's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited as a therapy of candidate for further clinical trials in the context of ischemic stroke.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
Publication statusPublished - 2007 Nov 13

Fingerprint

Niacinamide
Transient Ischemic Attack
Reperfusion
Brain Ischemia
Macrophages
Emigration and Immigration
T-Lymphocytes
Neutrophils
Brain Infarction
Brain
Melatonin
Intravenous Administration
Infarction
Monocytes
Ischemia
Immunohistochemistry
Stroke
Clinical Trials
Neurons
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{79d8813067114b959637d4bcfc538f5b,
title = "Nicotinamide reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats",
abstract = "We have previously shown that nicotinamide protects against energy depletion and decreases infarction in a rat model of cerebral ischemia [1, 2]. It is known that postischemic cell-mediated neuroinflammation exaggerates the initial brain insult caused by ischemia. Herein, we explored whether nicotinamide mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Nicotinamide (NICO, 500 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, NICO-treated animals resulted in significantly decreased macrophages (4.57(x105)±3.00 vs. 2.83(x105)±1.42) and T lymphocytes (0.74(x105)±0.57 vs. 0.28(x105)±1.42) in the bloodstream (P>0.05). Treatment with NICO also significantly decreased the cellular inflammatory response in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 55{\%} (P<0.01) and 66{\%} (P<0.01), respectively. In addition, NICO significantly decreased the population composition of T lymphocyte (CD3-positive/CD45-positive; P<0.001) by 39{\%}. This NICO-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction by 34{\%} (P<0.05) and improved surviving neurons in penumbral cortex and caudoputamen by 112{\%} (P<0.005) and 250{\%} (P<0.001), respectively. Thus, intravenous administration of NICO upon reperfusion effectively decreased the emigration of circulatory neutrophils, T-lymphocytes and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates nicotinamide's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited as a therapy of candidate for further clinical trials in the context of ischemic stroke.",
author = "Chen, {Tsung Ying} and Kuan, {Yu Hsiang} and Chen, {Hung Yi} and Lee, {Ming Yang} and E-Jian Lee",
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journal = "Journal of Cerebral Blood Flow and Metabolism",
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Nicotinamide reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. / Chen, Tsung Ying; Kuan, Yu Hsiang; Chen, Hung Yi; Lee, Ming Yang; Lee, E-Jian.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nicotinamide reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats

AU - Chen, Tsung Ying

AU - Kuan, Yu Hsiang

AU - Chen, Hung Yi

AU - Lee, Ming Yang

AU - Lee, E-Jian

PY - 2007/11/13

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N2 - We have previously shown that nicotinamide protects against energy depletion and decreases infarction in a rat model of cerebral ischemia [1, 2]. It is known that postischemic cell-mediated neuroinflammation exaggerates the initial brain insult caused by ischemia. Herein, we explored whether nicotinamide mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Nicotinamide (NICO, 500 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, NICO-treated animals resulted in significantly decreased macrophages (4.57(x105)±3.00 vs. 2.83(x105)±1.42) and T lymphocytes (0.74(x105)±0.57 vs. 0.28(x105)±1.42) in the bloodstream (P>0.05). Treatment with NICO also significantly decreased the cellular inflammatory response in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 55% (P<0.01) and 66% (P<0.01), respectively. In addition, NICO significantly decreased the population composition of T lymphocyte (CD3-positive/CD45-positive; P<0.001) by 39%. This NICO-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction by 34% (P<0.05) and improved surviving neurons in penumbral cortex and caudoputamen by 112% (P<0.005) and 250% (P<0.001), respectively. Thus, intravenous administration of NICO upon reperfusion effectively decreased the emigration of circulatory neutrophils, T-lymphocytes and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates nicotinamide's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited as a therapy of candidate for further clinical trials in the context of ischemic stroke.

AB - We have previously shown that nicotinamide protects against energy depletion and decreases infarction in a rat model of cerebral ischemia [1, 2]. It is known that postischemic cell-mediated neuroinflammation exaggerates the initial brain insult caused by ischemia. Herein, we explored whether nicotinamide mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Nicotinamide (NICO, 500 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, NICO-treated animals resulted in significantly decreased macrophages (4.57(x105)±3.00 vs. 2.83(x105)±1.42) and T lymphocytes (0.74(x105)±0.57 vs. 0.28(x105)±1.42) in the bloodstream (P>0.05). Treatment with NICO also significantly decreased the cellular inflammatory response in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 55% (P<0.01) and 66% (P<0.01), respectively. In addition, NICO significantly decreased the population composition of T lymphocyte (CD3-positive/CD45-positive; P<0.001) by 39%. This NICO-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction by 34% (P<0.05) and improved surviving neurons in penumbral cortex and caudoputamen by 112% (P<0.005) and 250% (P<0.001), respectively. Thus, intravenous administration of NICO upon reperfusion effectively decreased the emigration of circulatory neutrophils, T-lymphocytes and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates nicotinamide's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited as a therapy of candidate for further clinical trials in the context of ischemic stroke.

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