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

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/429505 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 35

Author(s):

Jintanaporn Wattanathorn ◽

Jinatta Jittiwat ◽

Terdthai Tongun ◽

Supaporn Muchimapura ◽

Kornkanok Ingkaninan

Keyword(s):

Cognitive Function ◽

Cerebral Ischemia ◽

Brain Damage ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Morris Water Maze Test ◽

Brain Infarct ◽

Ginger Rhizome ◽

The Brain

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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Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ

Cellular Physiology and Biochemistry ◽

10.1159/000447838 ◽

2016 ◽

Vol 39 (4) ◽

pp. 1339-1346 ◽

Cited By ~ 10

Author(s):

Lichun Pei ◽

Songyan Meng ◽

Weigang Yu ◽

Qiujun Wang ◽

Fangfang Song ◽

...

Keyword(s):

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Protein Level ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Luciferase Assay ◽

Cerebral Artery Occlusion

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in protecting against distinct brain damages, including ischemia. Our previous data have shown that the protein level of PPARγ is increased in the cortex after middle cerebral artery occlusion (MCAO); PPARγ up-regulation contributes to PPARγ activation and is effective in reducing ischemic damage to brain. However, the regulatory mechanism of PPARγ after focal cerebral ischemia in rats is still unclear. In this study, we evaluated the effect of microRNA on PPARγ in rats subjected to MCAO. Methods: Focal cerebral ischemia was established by surgical middle cerebral artery occlusion; the protein level of PPARγ was detected by Western blotting; the level of microRNA-383 (miR-383) was quantified by real-time PCR; the neurological outcomes were defined by infarct volume and neurological deficits. Luciferase assay was used to identify the luciferase activities of PPARγ and miR-383. Results: We showed here that miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and aggravated neurological damage. Administration of miR-383 antagomir had the opposite effects. Furthermore, we found that PPARγ protein was down-regulated by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat model of MCAO and in primary culture cells. Finally, we found that miR-383 suppressed the luciferase activity of the vector carrying the 3'UTR of PPARγ, whereas mutation of the binding sites relived the repressive effect of miR-383. Conclusion: Our study demonstrated that miR-383 may play a key role in focal cerebral ischemia by regulating PPARγ expression at the post-transcriptional level, and miR-383 may be a potential therapeutic target for stroke.

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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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Reduction of Infarct Volume by Magnesium after Middle Cerebral Artery Occlusion in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.170 ◽

1991 ◽

Vol 11 (6) ◽

pp. 1025-1030 ◽

Cited By ~ 122

Author(s):

Yoshio Izumi ◽

Simon Roussel ◽

Elisabeth Pinard ◽

Jacques Seylaz

Keyword(s):

Middle Cerebral Artery ◽

Cerebral Artery ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Triphenyltetrazolium Chloride ◽

Ischemic Brain ◽

Mca Occlusion ◽

Cerebral Artery Occlusion ◽

Hyperglycemic Effect

The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.

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Effect of One Week Treatment with Ginkgo biloba Extract (EGb761) on Ischemia-Induced Infarct Volume in Gerbils

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03001296 ◽

2003 ◽

Vol 31 (04) ◽

pp. 533-542 ◽

Cited By ~ 8

Author(s):

Shu-Ying Chung ◽

Ming-Fu Wang ◽

Jing-Ying Lin ◽

Ming-Cheng Lin ◽

Hui-Ming Liu ◽

...

Keyword(s):

Locomotor Activity ◽

Cerebral Ischemia ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Ginkgo Biloba ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Control Group ◽

Tetrazolium Chloride ◽

The Right

The present study was designed to evaluate the neuroprotective effects of Ginkgo biloba leaf extract (EGb761) in male gerbils subjected to focal cerebral ischemia produced by permanent occlusion of the right middle cerebral artery. In this study, gerbils were fed standard chow with or without EGb761 (100 mg/kg/day, i.g.) prior to cerebral ischemia for 1 week. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation. Infarct volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining 24 hours after initiation of cerebral ischemia. Results showed that the EGb761 group had significant reduction of infarct volume 4 and 6 mm from the frontal pole by 40% and 30%, respectively when compared to the control group ( p < 0.05). Mean locomotor activity of gerbils was reduced 24 hours after the occlusion of the MCA in both groups. However, there was no difference in locomotor activity between groups either 30 minutes before or 24 hours after the occlusion ( p < 0.05).

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Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199705000-00003 ◽

1997 ◽

Vol 17 (5) ◽

pp. 500-506 ◽

Cited By ~ 253

Author(s):

Wolf-R. Schäbitz ◽

Stefan Schwab ◽

Matthias Spranger ◽

Werner Hacke

Keyword(s):

Cerebral Ischemia ◽

Infarct Size ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Neurotrophic Factor ◽

Cortical Neurons ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Cerebral Artery Occlusion

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 μg/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls ( P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 ± 27.1 mm3 in BDNF-treated animals and 139.2 ± 56.4 mm3 in controls (mean ± SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 ± 7.1 mm3 in BDNF-treated animals and 37.9 ± 19.8 mm3 in controls (mean ± SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

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Ghrelin reduces cerebral ischemic injury in rats by reducing M1 microglia/macrophages

European Journal of Histochemistry ◽

10.4081/ejh.2022.3350 ◽

2022 ◽

Vol 66 (1) ◽

Author(s):

Rong Tian ◽

Gengsheng Mao

Keyword(s):

Cerebral Ischemia ◽

Brain Tissue ◽

Infarct Volume ◽

Neurological Function ◽

Tunel Staining ◽

Triphenyltetrazolium Chloride ◽

Ischemic Brain ◽

Tnf Α ◽

Ischemic Brain Tissue ◽

The Brain

The purpose of this study was to investigate the effect of Ghrelin on the polarization of microglia/ macrophages after cerebral ischemia (CI) in rats. 60 wild-type SD rats were randomly divided into sham group, CI group, CI+Ghrelin group, 20 rats in each group. The modified Longa suture method was used to establish the middle cerebral artery occlusion (MCAO) model in rats. Before surgery, Ghrelin was injected subcutaneously (100μg/kg, twice a day) for 4 consecutive weeks. After modeling, neurological function scores were performed with three behavioral experiments: mNSS score, Corner test, and Rotarod test, to evaluate the recovery of neurological function after Ghrelin treatment. At the same time, the brain tissues were collected and stained with 2,3,5-triphenyltetrazolium chloride (TTC) to detect the cerebral infarct volume. RT-qPCR was used to detect the expression of TNF-α and IL-1β in the ischemic brain tissue, and the TUNEL staining was used to detect the apoptosis of brain tissue. Flow cytometry was used to detect the percentage of M1 type microglia/macrophages which were isolated by trypsin digestion of fresh cerebral cortex. Then, the Western blotting and immunofluorescence method were used to detect the phosphorylation level of AKT (P-AKT) and AKT. Compared with the CI group, the neurological function of the rats in the CI+Ghrelin group was dramatically improved, and the cerebral infarction area was dramatically reduced. At the same time, the expression of TNF-α and IL-1β in the ischemic brain tissue of rats in the CI+Ghrelin group decreased, and the apoptotic cells in the brain tissue also decreased. Compared with the CI treatment group, the activation of M1 microglia/macrophages in the cortex of the ischemic side of the infarct and the peri-infarct area in the CI+Ghrelin group was dramatically inhibited. At the same time, the ratio of P-AKT/AKT of the brain tissue in the CI+Ghrelin group was dramatically higher than that of the CI group. In the rat cerebral ischemia model, Ghrelin can promote the repair of brain damage and the recovery of neurological function after ischemia. Its mechanism may be related to activating AKT to selectively reduce M1 microglia/macrophages, reducing inflammation and cell apoptosis in brain tissue.

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