Neuroprotective effect of antisense oligodeoxynucleotides in experimental intracerebral hemorrhage in rats

Tao-He-Cheng-Qi decoction (THCQ) is an effective traditional Chinese medicine used to treat intracerebral hemorrhage (ICH). This study was performed to investigate the possible neuroprotective effect of THCQ decoction on secondary brain damage in rats with intracerebral hemorrhage and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into five groups: the sham group, collagenase-induced ICH model group, THCQ low-dose (THCQ-L)-treated group, THCQ moderate-dose (THCQ-M)-treated group and THCQ high-dose (THCQ-H)-treated group. Following 3 days of treatment, behavioral changes and histopathological lesions in the brain were estimated. Untargeted metabolomics analysis with multivariate statistics was performed by using ultrahigh-performance liquid chromatography–mass spectrometry (UPLC-Q-Exactive Orbitrap MS). THCQ treatment at two dosages (5.64 and 11.27 g/kg·d) remarkably improved behavior (p < 0.05), brain water content (BMC) and hemorheology (p < 0.05) and improved brain nerve tissue pathology and inflammatory infiltration in ICH rats. Moreover, a metabolomic analysis demonstrated that the serum metabolic profiles of ICH patients were significantly different between the sham group and the ICH-induced model group. Twenty-seven biomarkers were identified that potentially predict the clinical benefits of THCQ decoction. Of these, 4 biomarkers were found to be THCQ-H group-specific, while others were shared between two clusters. These metabolites are mainly involved in amino acid metabolism and glutamate-mediated cell excitotoxicity, lipid metabolism-mediated oxidative stress, and mitochondrial dysfunction caused by energy metabolism disorders. In addition, a correlation analysis showed that the behavioral scores, brain water content and hemorheology were correlated with levels of serum metabolites derived from amino acid and lipid metabolism. In conclusion, the results indicate that THCQ decoction significantly attenuates ICH-induced secondary brain injury, which could be mediated by improving metabolic disorders in cerebral hemorrhage rats.

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Activation of silent information regulator 1 exerts a neuroprotective effect after intracerebral hemorrhage by deacetylating NF‐κB/p65

Journal of Neurochemistry ◽

10.1111/jnc.15258 ◽

2020 ◽

Author(s):

Hong‐Ji Deng ◽

Chen‐Hui Zhou ◽

Li‐Tian Huang ◽

Liang‐Bao Wen ◽

Meng‐Liang Zhou ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Neuroprotective Effect ◽

Silent Information Regulator 1

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The neuroprotective effect of apelin-13 in a mouse model of intracerebral hemorrhage

Neuroscience Letters ◽

10.1016/j.neulet.2016.06.046 ◽

2016 ◽

Vol 628 ◽

pp. 219-224 ◽

Cited By ~ 14

Author(s):

Haijun Bao ◽

Xiaofang Yang ◽

YuXiu Huang ◽

Haiyang Qiu ◽

Genping Huang ◽

...

Keyword(s):

Mouse Model ◽

Intracerebral Hemorrhage ◽

Neuroprotective Effect

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Glibenclamide Attenuates Neuroinflammation and Promotes Neurological Recovery After Intracerebral Hemorrhage in Aged Rats

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.729652 ◽

2021 ◽

Vol 13 ◽

Author(s):

Bing Jiang ◽

Ying Zhang ◽

Yan Wang ◽

Zheng Li ◽

Qianwei Chen ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Neuroprotective Effect ◽

The Elderly ◽

Common Disease ◽

Secondary Brain Injury ◽

Sulfonylurea Receptor ◽

Aged Rats ◽

Neurological Outcomes ◽

Iκb Kinase ◽

Trpm4 Channel

Intracerebral hemorrhage (ICH) is a common disease in the elderly population. Inflammation following ICH plays a detrimental role in secondary brain injury, which is associated with a poor prognosis of patients with ICH, and no efficient pharmacological preventions are available. Here, we investigated the effects of glibenclamide (GLC) on neuroinflammation in an autoblood-induced aged rat (18 months old) model of ICH. Rats were randomized into the sham, vehicle, and GLC groups. First, we investigated the expression level of sulfonylurea receptor 1 (Sur1) surrounding the hematoma after ICH. Then, neurological scores were calculated, and water maze tests, brain water content analysis, western blotting, and immunofluorescence assays were implemented to detect the neuroprotective effect of GLC. The expression of the Sur1-Trpm4 channel was significantly increased in the perihematomal tissue following ICH in aged rats. The GLC administration effectively reduced brain edema and improved neurofunction deficits following ICH. In addition, GLC increased the expression of brain-derived neurotrophic factors and decreased the expression of proinflammatory factors [tumor necrosis factor (TNF)-α,interleukin (IL)-1, and IL-6]. Moreover, GLC markedly reduced Ikappa-B (IκB) kinase (IKK) expression in microglia and nuclear factor (NF)-κB-P65 levels in perihematomal tissue. GLC ameliorated ICH-induced neuroinflammation and improved neurological outcomes in aged rats. In part, GLC may exert these effects by regulating the NF-κB signaling pathway through the Sur1-Trpm4 channel.

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Extract ofAntrodia camphorataExerts Neuroprotection against Embolic Stroke in Rats without Causing the Risk of Hemorrhagic Incidence

The Scientific World JOURNAL ◽

10.1155/2014/686109 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Ye-Ming Lee ◽

Chiu-Yun Chang ◽

Ting-Lin Yen ◽

Pitchairaj Geraldine ◽

Chang-Chou Lan ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Bleeding Time ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Blood Perfusion ◽

Embolic Stroke ◽

High Dose ◽

Gastric Bleeding ◽

Triphenyltetrazolium Chloride ◽

Occlusion Time

In this study, the neuroprotective effect of an extract ofAntrodia camphorata(A. camphorata), a fungus commonly used in Chinese folk medicine for treatment of viral hepatitis and cancer, alone or in combination with aspirin was investigated in a rat embolic stroke model. An ischemic stroke was induced in rats by a selective occlusion of the middle cerebral artery (MCA) with whole blood clots and then orally treated withA. camphorata(0.25 and 0.75 g/kg/day) alone and combined with aspirin (5 mg/kg/day). Sixty days later, the brains were removed, sectioned, and stained with triphenyltetrazolium chloride and analysed by a commercial image processing software program. Brain infarct volume, neurobehavioral score, cerebral blood perfusion, and subarachnoid and intracerebral hemorrhage incidence were perceived. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring hemoglobin (Hb) content during intracerebral hemorrhage and gastric bleeding, prothrombin time (PT), and occlusion time (OT) after oral administration. Posttreatment with high doseA. camphoratasignificantly reduced infarct volume and improved neurobehavioral score (P< 0.05). SinceA. camphorataalone or with aspirin did not alter the Hb level, this treatment is safe and does not cause hemorrhagic incident. Remarkably, the combination ofA. camphorataand aspirin did not show a significant effect on the bleeding time, PT and OT increase suggesting thatA. camphoratamay have the neuroprotective effect without the prolongation of bleeding time or coagulation time. From these observations, we suggest that combinative therapy ofA. camphorataand aspirin might offer enhanced neuroprotective efficacies without increasing side effects.

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