scholarly journals Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury

2016 ◽  
Vol 120 (3) ◽  
pp. 328-333 ◽  
Author(s):  
Chun Li ◽  
Hong Sun ◽  
Denise M. Arrick ◽  
William G. Mayhan
Keyword(s):  
Cerebral Cortex ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Neurological Deficits ◽  
Control Group ◽  
Nicotine Exposure ◽  
Chronic Nicotine ◽  
Transient Focal Cerebral Ischemia

Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg·kg−1·day−1) for 4 wk via an implanted subcutaneous osmotic minipump and subjected to a 2-h middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 h of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase but significantly decreased MnSOD and uncoupling protein-2 (UCP-2) in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a preexisting oxidative stress via decreasing of MnSOD and UCP-2.

The antioxidant effects of Joongpoongtang 05 on brain injury after transient focal cerebral ischemia in rats

2011 ◽  
Vol 65 (2) ◽  
pp. 322-329 ◽  
Author(s):  
Hyo Won Jung ◽  
Ramalingam Mahesh ◽  
Hyo Sang Bae ◽  
Young Ho Kim ◽  
Jong Seong Kang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Transient Focal Cerebral Ischemia ◽  
Antioxidant Effects

Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury

2004 ◽  
Vol 286 (6) ◽  
pp. H2442-H2451 ◽  
Author(s):  
Ikuyo Kusaka ◽  
Gen Kusaka ◽  
Changman Zhou ◽  
Mami Ishikawa ◽  
Anil Nanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Focal Cerebral Ischemia ◽  
Lipid Hydroperoxide ◽  
Neurological Deficits ◽  
Sprague Dawley

The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT1-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT1-R antagonist candesartan (0.5 mg·kg−1·day−1) for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats ( n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91phox and p22phox mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase gp91phox and p22phox mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91phox and p22phox, decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT1-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.

scholarly journals Induction of Type 2 Iodothyronine Deiodinase in Astrocytes after Transient Focal Cerebral Ischemia in the Rat

2005 ◽  
Vol 25 (4) ◽  
pp. 468-476 ◽  
Author(s):  
Isabelle Margaill ◽  
Julien Royer ◽  
Dominique Lerouet ◽  
Martine Ramaugé ◽  
Claude Le Goascogne ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Thyroid Hormones ◽  
Focal Cerebral Ischemia ◽  
Iodothyronine Deiodinase ◽  
Reverse Transcription Pcr ◽  
Transient Focal Cerebral Ischemia ◽  
Ipsilateral Striatum ◽  
Future Work

This study investigated the expression of deiodinases of thyroid hormones in the rat brain after transient occlusion of the middle cerebral artery. The activity of type 2 deiodinase (D2), which catalyzes the deiodination of thyroxine into the more active thyroid hormone 3,5,3′-triiodothyronine, was strongly increased by cerebral ischemia at 6 and 24 hours in the striatum and at 24 hours in the cerebral cortex. The activity of type 3 deiodinase, which catalyzes the inactivation of thyroid hormones, was not affected by ischemia. In situ hybridization showed, as soon as 6 hours, an upregulation of the expression of D2 mRNA in the ipsilateral striatum, which disappeared at 24 hours. In the ipsilateral cortex, the induction of D2 mRNA started at 6 hours, was increased at 24 hours and finally declined at 72 hours. These results were confirmed by reverse transcription-PCR for D2 mRNA in the striatum and cerebral cortex. The upregulation of D2 mRNA after ischemia was mainly localized in astrocytic cell bodies. These results show that D2 is rapidly induced in astrocytes after ischemic stroke. Future work will include the exploration of the role of the upregulation of this enzyme, responsible for local 3,5,3′-triiodothyronine production as a neuroprotective mechanism in the brain.

scholarly journals Inducible Nitric Oxide Synthase Does Not Mediate Brain Damage after Transient Focal Cerebral Ischemia in Mice

2007 ◽  
Vol 28 (3) ◽  
pp. 526-539 ◽  
Author(s):  
Harald Prüss ◽  
Konstantin Prass ◽  
Leyli Ghaeni ◽  
Milan Milosevic ◽  
Claudia Muselmann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Inos Mrna ◽  
Wild Type ◽  
Transient Focal Cerebral Ischemia ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide produced by the inducible nitric oxide synthase (iNOS) is believed to participate in the pathogenic events after cerebral ischemia. In this study, we examined the expression of iNOS in the brain after transient focal cerebral ischemia in mice. We detected differential expression of exons 2 and 3 of iNOS mRNA (16-fold upregulation at 24 to 72 h after middle cerebral artery occlusion, MCAO) compared with exons 6 to 8, 12 to 14, 21 to 22, and 26 to 27 (2- to 5-fold upregulation after 72 and 96 h), which would be compatible with alternative splicing. Expression levels of iNOS mRNA were too low for detection by the Northern blot analysis. Using specific antibodies, we did not detect any iNOS immunoreactivity in the mouse brain 1 to 5 days after MCAO, although we detected iNOS immunoreactivity in the lungs of mice with stroke-associated pneumonia, and in mouse and rat dura mater after lipopolysaccharide administration. In chimeric iNOS-deficient mice transplanted with wild-type bone marrow (BM) cells expressing the green fluorescent protein (GFP) or in wild-type mice transplanted with GFP+ iNOS-deficient BM cells, no expression of iNOS was detected in GFP+ leukocytes invading the ischemic brain or in resident brain cells. Moreover, both experimental groups did not show any differences in infarct size. Analysis of three different strains of iNOS-deficient mice and wild-type controls confirmed that infarct size was independent of iNOS deletion, but strongly confounded by the genetic background of mouse strains. In conclusion, our data suggest that iNOS is not a universal mediator of brain damage after cerebral ischemia.

Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats

2000 ◽  
Vol 853 (1) ◽  
pp. 68-73 ◽  
Author(s):  
Roland Veltkamp ◽  
David S. Warner ◽  
Ferenc Domoki ◽  
Ann D. Brinkhous ◽  
James F. Toole ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Hyperbaric Oxygen ◽  
Focal Cerebral Ischemia ◽  
Behavioral Deficit ◽  
Transient Focal Cerebral Ischemia
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