Zingiber officinaleMitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17720371 ◽

2017 ◽

Vol 38 (6) ◽

pp. 1010-1020 ◽

Cited By ~ 3

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.

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Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2010000400021 ◽

2010 ◽

Vol 68 (4) ◽

pp. 592-596 ◽

Cited By ~ 8

Author(s):

Daniela Pretti da Cunha Tirapelli ◽

Carlos Gilberto Carlotti Junior ◽

João Pereira Leite ◽

Luis Fernando Tirapelli ◽

Benedicto Oscar Colli

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Hsp70 Expression ◽

Tetrazolium Chloride ◽

A Cell ◽

Shock Proteins ◽

H Protein

Heat shock proteins (HSPs) are molecular chaperones that bind to other proteins to shepherd them across membranes and direct them to specific locations within a cell. Several injurious stimuli can induce Hsp70 expression, including ischemia. This study aimed to investigate the pattern of expression of protein (immunohistochemistry) and gene (real-time PCR) Hsp70 in experimental focal cerebral ischemia in rats by occlusion of the middle cerebral artery for 1 hour and the role of neuroprotection with hypothermia (H) and ketoprofen (K). The infarct volume was measured using morphometric analysis defined by triphenyl tetrazolium chloride. It was observed increases in the protein (p=0.0001) and gene (p=0.0001) Hsp70 receptor in the ischemic areas that were reduced by H (protein and gene: p<0.05), K (protein: p<0.001), and H+K (protein: p<0.01 and gene: p<0.05). The Hsp70 increases in the ischemic area suggests that the Hsp70-mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, H and K are directly involved with the Hsp70.

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Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

Reports of Morphology ◽

10.31393/morphology-journal-2018-24(3)-09 ◽

2018 ◽

Vol 24 (3) ◽

pp. 58-64

Author(s):

O.I. Savchuk ◽

G.G. Skibo

Keyword(s):

Cerebral Ischemia ◽

Brain Damage ◽

Nervous Tissue ◽

Focal Cerebral Ischemia ◽

Tactile Sensitivity ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Ischemic Period ◽

The Brain ◽

Occlusion Period

The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.01084.2017 ◽

2018 ◽

Vol 125 (1) ◽

pp. 49-57 ◽

Cited By ~ 3

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.

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Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia

Behavioural Neurology ◽

10.1155/2018/5050469 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 7

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.

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Delayed Treatment with Nicotinamide Inhibits Brain Energy Depletion,Improves Cerebral Microperfusion, Reduces Brain Infarct Volume, but does not Alter Neurobehavioral Outcome Following Permanent Focal Cerebral Ischemia in Sprague Dawley Rats

Current Neurovascular Research ◽

10.2174/156720206778018749 ◽

2006 ◽

Vol 3 (3) ◽

pp. 203-213 ◽

Cited By ~ 14

Author(s):

E-Jian Lee ◽

Tian-Shung Wu ◽

Guan-Liang Chang ◽

Chia-Ying Li ◽

Tsung-Ying Chen ◽

...

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Sprague Dawley ◽

Brain Infarct ◽

Energy Depletion ◽

Delayed Treatment ◽

Sprague Dawley Rats ◽

Brain Energy ◽

Neurobehavioral Outcome

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

Stroke ◽

10.1161/str.44.suppl_1.atp109 ◽

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.

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

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03000734 ◽

2003 ◽

Vol 31 (01) ◽

pp. 71-77 ◽

Cited By ~ 23

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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