scholarly journals Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Min Jae Kim ◽  
Seo-Yeon Lee ◽  
Ji Young Hwang ◽  
Hyunha Kim ◽  
Ki-Tae Ha ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Mouse Model ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Immunohistochemical Analysis ◽  
Medicinal Herbs ◽  
Neurological Deficits ◽  
Dependent Manner

Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4) was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg), while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

Abstract TP109: Impact of ATP-Induced Mild Hypothermia on Focal Cerebral Ischemia in Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Meijuan Zhang ◽  
Wenjin Li ◽  
Rehana K Leak ◽  
Jun Chen ◽  
Feng Zhang
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Body Temperature ◽  
Mild Hypothermia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Core Body Temperature ◽  
Artery Occlusion ◽  
Dependent Manner

Brain ischemia is a devastating disorder without effective therapies. One of the most promising approaches to attenuate ischemic brain injury is mild hypothermia. Recent studies show that adenosine nucleotides can induce hypothermia in mice. The purpose of the present study was to test the hypothesis that ATP, a common form of energy currency, induces mild hypothermia in rats and reduces brain injury following focal cerebral ischemia. ATP solution was dissolved in water and intraperitoneally injected; and focal stroke was induced by a suture model of middle cerebral artery occlusion and ischemic outcomes were evaluated within 24 hr. We found that injections of ATP lowered core body temperature in a dose-dependent manner; the dose appropriate for subsequent experiments was 2 g/kg as it reduced temperature to the range of mild hypothermia for approximately 7 hours. While intravenous injection of ATP was less effective in lowering body temperature. However, when ATP-induced hypothermia was applied to stroke, a neuroprotective effect was not observed. In contrast, the infarct volume grew even larger in ATP-treated rats. Not surprisingly, this was accompanied by an increased rate of seizure events, hemorrhagic transformation, and higher mortality. Continuous monitoring of physiological parameters revealed that ATP severely reduced heartbeat rate and blood pressure. ATP also raised blood glucose to dangerous levels and this was accompanied by severe acidosis and hypocalcemia. Western blotting showed that ATP treatment decreased levels of both phospho-Akt and total-Akt in the ischemic cortex. Our results reveal that, despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke, as it is associated with exaggerated ischemic outcomes and dangerous systemic side effects.

scholarly journals Neuronal expression of the mitochondrial protein prohibitin confers profound neuroprotection in a mouse model of focal cerebral ischemia

2017 ◽  
Vol 38 (6) ◽  
pp. 1010-1020 ◽  
Author(s):  
Anja Kahl ◽  
Corey J Anderson ◽  
Liping Qian ◽  
Henning Voss ◽  
Giovanni Manfredi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Mitochondrial Protein ◽  
Motor Impairment ◽  
Cell Types ◽  
Viral Gene ◽  
Sensory Motor ◽  
The Brain

The mitochondrial protein prohibitin (PHB) has emerged as an important modulator of neuronal survival in different injury modalities . We previously showed that viral gene transfer of PHB protects CA1 neurons from delayed neurodegeneration following transient forebrain ischemia through mitochondrial mechanisms. However, since PHB is present in all cell types, it is not known if its selective expression in neurons is protective, and if the protection occurs also in acute focal ischemic brain injury, the most common stroke type in humans. Therefore, we generated transgenic mice overexpressing human PHB1 specifically in neurons (PHB1 Tg). PHB1 Tg mice and littermate controls were subjected to transient middle cerebral artery occlusion (MCAo). Infarct volume and sensory-motor impairment were assessed three days later. Under the control of a neuronal promoter (CaMKIIα), PHB1 expression was increased by 50% in the forebrain and hippocampus in PHB1 Tg mice. The brain injury produced by MCAo was reduced by 63 ± 11% in PHB1 Tg mice compared to littermate controls. This reduction was associated with improved sensory-motor performance, suggesting that the salvaged brain remains functional. Approaches to enhance PHB expression may be useful to ameliorate the devastating impact of cerebral ischemia on the brain.

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.

Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury

1989 ◽  
Vol 256 (2) ◽  
pp. H589-H593 ◽  
Author(s):  
T. H. Liu ◽  
J. S. Beckman ◽  
B. A. Freeman ◽  
E. L. Hogan ◽  
C. Y. Hsu
Keyword(s):  
Hydrogen Peroxide ◽  
Superoxide Dismutase ◽  
Polyethylene Glycol ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Free Radical Scavengers ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.

Abstract T MP53: Whole Blood Immuno-Chromatography for Rapid Detection of Cerebral Ischemia in the Pre-Hospital Setting

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Luther C Pettigrew ◽  
Melissa A Bradley-Whitman ◽  
Mark A Lovell
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Whole Blood ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Hospital Setting ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Ischemic Reperfusion ◽  
Arterial Blood

BACKGROUND: Pre-hospital detection of ischemic brain injury will exclude stroke mimics and refine patient triage. Using “dipstick” immuno-chromatography, we validated a rapid-sequence method to identify visinin-like protein-1 (VILIP-1), a neuronal injury marker, in blood sampled after focal cerebral ischemia in rats. METHODS: Transgenic (Tg) rats were constructed to over-express tumor necrosis factor-alpha (TNFα) in brain. Suture-occlusion of the middle cerebral artery (MCAO) was performed in TNFα-Tg animals and wild type (WT) littermates for 1 hr. Arterial blood was sampled at pre-ischemic baseline, after 60 min of MCAO, and at 15 min or 24 hrs of post-ischemic reperfusion. VILIP-1 immuno-reactivity was normalized to pre-ischemic baseline and compared to sham-ischemic animals. Brain infarct volume was measured at 24 hrs. VILIP-1 immuno-reactivity was then correlated with infarct volume to derive Pearson product moment. RESULTS: VILIP-1 immuno-reactivity was increased after 24 hrs of post-ischemic reperfusion in TNFα-Tg animals (133 ± 13 [SD]% of baseline) compared to sham-ischemic rats (100 ± 22; p ≤ 0.05; ANOVA; n = 5 per group). At 15 min (159 ± 36%) and 24 hrs (above), VILIP-1 expression was greater than pre-ischemic baseline ( p ≤ 0.05). Immuno-reactivity of VILIP-1 at 15-min post-ischemic reperfusion was strongly correlated with infarct volume measured at 24 hrs in TNFα-Tg rats (Pearson 0.79; p ≤ 0.01). CONCLUSIONS: Whole blood immuno-chromatography of VILIP-1 is feasible and correlates positively with infarct volume measured at 24 hrs in the rat. These promising results underscore the need to study VILIP-1 immuno-reactivity as an indicator of ischemic brain injury in the pre-hospital setting.

scholarly journals Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

2018 ◽  
Vol 125 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Chun Li ◽  
Hong Sun ◽  
Guodong Xu ◽  
Kimberly D. McCarter ◽  
Jiyu Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Ischemic Brain Damage ◽  
Mitochondrial Oxidative Stress ◽  
Ischemic Brain

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg−1·day−1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg−1·day−1ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation.NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

scholarly journals Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanhua Qin ◽  
Weiming Hu ◽  
Yang Yang ◽  
Zhiying Hu ◽  
Weiyun Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Tunel Staining ◽  
Cox 2

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5′-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrement in proteins Bcl-2 and COX-2 expressions. On the basis of our results, we hypothesize DAHP to have a neuroprotective function against focal cerebral ischemia and might attenuate brain injury by decreasing reactive oxygen species (ROS) production, subsequently inhibiting apoptosis.

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.

Long-Term Administration of Polygonum multiflorum Thunb: Reduces Cerebral Ischemia-induced Infarct Volume in Gerbils

2003 ◽  
Vol 31 (01) ◽  
pp. 71-77 ◽  
Author(s):  
Yin-Ching Chan ◽  
Ming-Fu Wang ◽  
Ya-Ching Chen ◽  
Dar-Yu Yang ◽  
Ming-Shih Lee ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ethanol Extract ◽  
Polygonum Multiflorum ◽  
Triphenyltetrazolium Chloride ◽  
Term Administration ◽  
The Brain

Focal cerebral ischemia was produced by an occlusion of the middle cerebral artery for 1, 3 and 24 hours in gerbils. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride (TTC) transcardiac perfusion 24 hours after cerebral ischemia. Significant and consistent infarct sizes were produced in gerbils subjected to 24-hour occlusion of the middle cerebral arterey when compared to the 1 and 3-hour occlusion groups. Long term pretreatment of the 50% ethanol extract of Polygonum multiflorum Thunb. for 2 weeks significantly reduced the infarct volume by 50% as compared to that of the 24-hour occlusion group. The results revealed that long term pretreatment of Polygonum multiflorum Thunb. may protect the brain against focal cerebral ischemia.

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