scholarly journals Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Li ◽  
Dou Wang ◽  
Bingbing Zhao ◽  
Yongmei Yan
Keyword(s):  
Hippocampal Neurons ◽  
Artery Occlusion ◽  
Immunofluorescence Assay ◽  
Antidepressant Effect ◽  
Tunel Staining ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Protein Levels ◽  
Swimming Test ◽  
Cerebral Artery Occlusion

Background.The neurotrophic pathway regulated by the brain-derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear.Objective.This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway.Methods.After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive-like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5-HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p-ERK/ERK, and p-CREB/CREB in the cortical and hippocampal regions were tested by Western blot.Results.The depressive-like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5-HT, NE, and BDNF and recovered the protein levels of p-ERK/ERK, p-CREB/CREB, and BDNF in the cortical and hippocampal regions.Conclusion.These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.

scholarly journals Jieyu Anshen Granule, a Chinese Herbal Formulation, Exerts Effects on Poststroke Depression in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yuan Du ◽  
Jian Ruan ◽  
Leiming Zhang ◽  
Fenghua Fu
Keyword(s):  
Underlying Mechanism ◽  
Artery Occlusion ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Depression And Anxiety ◽  
Poststroke Depression ◽  
Antidepressive Effect ◽  
Newborn Neurons ◽  
Cerebral Artery Occlusion ◽  
Inflammation Cytokines

Jieyu Anshen granule (JY) is a traditional Chinese medicine formula for treating depression and anxiety. The aim of the study was to observe the effects of JY on poststroke depression (PSD) and investigate the underlying mechanism. PSD rat model was developed by middle cerebral artery occlusion following chronic unpredictable mild stress in conjunction with isolation rearing. We performed behavioral tests, Western blot, ELISA, and BrdU/NeuN staining. Treatment with JY showed significant antidepressant effect in open-field and sucrose preference tests, as well as significant improvement in beam-walking, cylinder, grip strength, and water maze tests. In addition, treatment with JY could restore the levels of neurotransmitters and decrease the levels of hormone and inflammation cytokines in serum and brain. Treatment with JY also showed significant regulation in the expression of neurotransmitter receptors and NF-κB/IκB-α signaling in the prefrontal cortex and hippocampus. Moreover, the numbers of newborn neurons in the hippocampus were increased by treatment with JY. Our results suggest that JY could ameliorate PSD and improve the neurological and cognitive functions. The antidepressive effect may be associated with the modulation of JY on monoamine system, neuroendocrine, neuroinflammation, and neurogenesis.

scholarly journals Buyang Huanwu Decoction Ameliorates Poststroke Depression via Promoting Neurotrophic Pathway Mediated Neuroprotection and Neurogenesis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Lin Luo ◽  
Shuhua Deng ◽  
Jian Yi ◽  
Sainan Zhou ◽  
Yan She ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Artery Occlusion ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Buyang Huanwu Decoction ◽  
Sucrose Preference Test ◽  
Cerebral Artery Occlusion

Objective.The aim of the present research is to investigate the therapeutic effect of Buyang Huanwu Decoction (BHD) in poststroke depression (PSD) animal model and illustrate its underlying mechanism via promoting neurotrophic pathway mediated neuroprotection and neurogenesis.Methods.To induce PSD rat model, isolation housed rats that received middle cerebral artery occlusion (MCAO) surgery successively suffered from chronic mild stress (CMS) treatment for consecutive twenty-one days. Meanwhile, rats were correspondingly given vehicle, BHD, and fluoxetine. Then, neurologic function was scored and depressive-like behaviors were assessed by sucrose preference test, locomotor activity, novelty-suppressed feeding test, and forced swim test. Thereafter, the neuroprotection and neurogenesis related molecular markers and signaling were detected.Results.We firstly observed a significant neurological function recovery and antidepressants effect of BHD after MCAO together with CMS treatment. Our study also found that treatment with BHD and fluoxetine can significantly rescue neurons from apoptosis and promote neurogenesis in the CA3 and DG regions in the hippocampus. Notably, BHD and fluoxetine treatment can activate BDNF/ERK/CREB signaling.Conclusion.The results suggest that BHD is a promising candidate for treating PSD. Its curative effects can be attributed to neurotrophic pathway mediated neuroprotection and neurogenesis.

scholarly journals The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

2021 ◽  
Author(s):  
Yong-Ming Zhu ◽  
Liang Lin ◽  
Chao Wei ◽  
Yi Guo ◽  
Yuan Qin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Glial Scar ◽  
Scar Formation ◽  
Reactive Astrocytes ◽  
Interacting Protein ◽  
Protein Levels ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

Abstract WP265: Interferon-inducible Protein 10 Increases following Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Hilary A Seifert ◽  
Lisa A Collier ◽  
Stanley A Benkovic ◽  
Alison E Willing ◽  
Keith R Pennypacker
Keyword(s):  
Time Course ◽  
Neutralizing Antibody ◽  
Artery Occlusion ◽  
T Helper ◽  
Protein Levels ◽  
Organ Systems ◽  
Inducible Protein ◽  
Cerebral Artery Occlusion ◽  
The Brain ◽  
Interferon Inducible Protein

Objective: The splenic response to injury furthers cellular degeneration as its removal is protective in ischemic injuries to several organ systems including the brain. Previously, we have shown that the proinflammatory cytokine interferon gamma (IFNg), which activates microglia/macrophages, is elevated in the spleen and the brain following permanent middle cerebral artery occlusion (MCAO). IFNg induces the production of interferon-inducible protein 10 (IP-10) which further propagates the inflammatory response. Therefore, we investigated the expression of IP-10 in the brain and spleen following ischemic stroke. Hypothesis: IFNg production in the brain and the spleen results in elevated levels of IP-10 in the same tissues post-MCAO. Methods: A time course was conducted to investigate splenic and brain protein levels of IP-10 in rats over time following MCAO and sham-MCAO (n≥3). In a second experiment, rats were administered an IFNg neutralizing antibody following MCAO with a survival time of 96 h: vehicle control (n=4), goat IgG 5μg (n=7), and IFNg antibody 5μg (n=7). Spleens and brains were collected for all groups. Results: IP-10 levels were significantly elevated in the brain at 72 and 96 h post-MCAO (p<0.01) compared to naïve brains. In the spleen IP-10 levels become significantly elevated at 24 h and remain elevated out to 96 h post-MCAO (p<0.0007) compared to naïve spleens. Administration of a neutralizing antibody directed against IFNg significantly decreased IP-10 levels in the brain (p<0.009) but did not affect IP-10 levels in the spleen. Conclusion: These results demonstrate that increased production of IFNg results in elevated levels of IP-10 in both the spleen and the brain following stroke. However, administration of a neutralizing antibody against IFNg decreased the amount of IP-10 in the brain. Levels of IFNg and IP-10 in the brain increase at the same time following stroke. Based on these data, IFNg propagates a proinflammatory T helper cell response to stroke through IP-10. Inhibition of this signaling could reduce neuroinflammation thereby improving stroke outcome.

scholarly journals Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Idriss Ali Abdoulaye ◽  
Shan-shan Wu ◽  
Enkhmurun Chibaatar ◽  
Da-fan Yu ◽  
Kai Le ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Brain Regions ◽  
Artery Occlusion ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Poststroke Depression ◽  
Hippocampal Dentate Gyrus ◽  
Downstream Signaling ◽  
Antidepressant Effects

Background. Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods. To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results. Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions. These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine’s lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

scholarly journals Induction Profile of MANF/ARMET by Cerebral Ischemia and its Implication for Neuron Protection

2009 ◽  
Vol 30 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Yong-Qiang Yu ◽  
Lian-Cheng Liu ◽  
Fa-Cai Wang ◽  
Yan Liang ◽  
Da-Qin Cha ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Er Stress ◽  
Focal Cerebral Ischemia ◽  
Early Stage ◽  
Artery Occlusion ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Homologous Protein ◽  
Inducible Protein ◽  
Cerebral Artery Occlusion

Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion with a suture; ischemic lesions were assessed by magnetic resonance imaging and histology; neuronal apoptosis was determined by TUNEL staining; the expressions of proteins were measured by immunohistochemistry, immunofluorescent labeling, and Western blotting. ARMET was found to be extensively upregulated in ischemic regions in a time-dependent manner. The expression of ARMET was neuronal in all examined structures in response to the ischemic insult. We also found that ARMET expression is earlier and more sensitive to ischemic stimulation than C/EBP homologous protein (CHOP). ER stress agent tunicamycin induced ARMET and CHOP expressions in the primary cultured neurons. Treatment with recombinant human ARMET promoted neuron proliferation and prevented from neuron apoptosis induced by tunicamycin. These results suggest that cerebral ischemia-induced ARMET expression may be protective to the neurons.

scholarly journals Postischemic Anhedonia Associated with Neurodegenerative Changes in the Hippocampal Dentate Gyrus of Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-20
Author(s):  
Jiro Kasahara ◽  
Hiroto Uchida ◽  
Kenta Tezuka ◽  
Nanae Oka
Keyword(s):  
Dentate Gyrus ◽  
Neuronal Loss ◽  
Immunohistochemical Analysis ◽  
Granular Cell ◽  
Artery Occlusion ◽  
Poststroke Depression ◽  
Hippocampal Dentate Gyrus ◽  
Antidepressant Imipramine ◽  
Effective Use ◽  
Cerebral Artery Occlusion

Poststroke depression is one of the major symptoms observed in the chronic stage of brain stroke such as cerebral ischemia. Its pathophysiological mechanisms, however, are not well understood. Using the transient right middle cerebral artery occlusion- (MCAO-, 90 min) operated rats as an ischemia model in this study, we first observed that aggravation of anhedonia spontaneously occurred especially after 20 weeks of MCAO, and it was prevented by chronic antidepressants treatment (imipramine or fluvoxamine). The anhedonia specifically associated with loss of the granular neurons in the ipsilateral side of hippocampal dentate gyrus and was also prevented by an antidepressant imipramine. Immunohistochemical analysis showed increased apoptosis inside the granular cell layer prior to and associated with the neuronal loss, and imipramine seemed to recover the survival signal rather than suppressing the death signal to prevent neurons from apoptosis. Proliferation and development of the neural stem cells were increased transiently in the subgranular zone of both ipsi- and contralateral hippocampus within one week after MCAO and then decreased and almost ceased after 6 weeks of MCAO, while chronic imipramine treatment prevented them partially. Overall, our study suggests new insights for the mechanistic correlation between poststroke depression and the delayed neurodegenerative changes in the hippocampal dentate gyrus with effective use of antidepressants on them.

scholarly journals Lipidomic Profiling of Ipsilateral Brain and Plasma after Celastrol Post-Treatment in Transient Middle Cerebral Artery Occlusion Mice Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4124
Author(s):  
Maozhu Liu ◽  
Mengyuan Chen ◽  
Ying Luo ◽  
Hong Wang ◽  
Haifeng Huang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Sphingolipid Metabolism ◽  
Tunel Staining ◽  
Cerebral Artery Occlusion

Celastrol, a pentacyclic triterpene isolated from the traditional Chinese medicine Tripterygium wilfordii Hook. F., exhibits effectiveness in protection against multiple central nervous system (CNS) diseases such as cerebral ischemia, but its influence on lipidomics still remains unclear. Therefore, in the present study, the efficacy and potential mechanism of celastrol against cerebral ischemia/reperfusion (I/R) injury were investigated based on lipidomics. Middle cerebral artery occlusion (MCAO) followed by reperfusion was operated in mice to set up a cerebral I/R model. TTC staining and TUNEL staining were used to evaluate the therapeutic effect of celastrol. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS) was employed for lipidomics analysis in ipsilateral hemisphere and plasma. Celastrol remarkably reduced cerebral infarct volume and apoptosis positive cells in tMCAO mice. Furthermore, lipidomics analysis showed that 14 common differentially expressed lipids (DELs) were identified in brain and five common DELs were identified in plasma between the Sham, tMCAO and Celastrol-treated tMCAO groups. Through enrichment analysis, sphingolipid metabolism and glycerophospholipid metabolism were demonstrated to be significantly enriched in all the comparison groups. Among the DELs, celastrol could reverse cerebral I/R injury-induced alteration of phosphatidylcholine, phosphatidylethanolamine and sulfatide, which may be responsible for the neuroprotective effect of celastrol. Our findings suggested the neuroprotection of celastrol on cerebral I/R injury may be partially associated with its regulation of lipid metabolism.

scholarly journals Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shuo Jiang ◽  
Zui Shen ◽  
Wenlin Xu
Keyword(s):  
Synaptic Plasticity ◽  
Global Mental Health ◽  
Hippocampal Slices ◽  
Preference Test ◽  
Long Term Potentiation ◽  
Antidepressant Effect ◽  
Feeding Time ◽  
Mild Stress ◽  
Protein Levels ◽  
Behavior Of Rats

Objective. Depression is a global mental health problem with high disability rate, which brings a huge disease burden to the world. Electroacupuncture (EA) has been shown to be an effective method for the treatment of depression. However, the mechanism underling the antidepressant effect of EA has not been clearly clarified. The change of synaptic plasticity is the focus in the study of antidepressant mechanism. This study will observe the effect of EA on LTP of hippocampal synaptic plasticity and explore its possible mechanism. Methods. The depression-like behavior rat model was established by chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) was used to treat the depressed rats. The depression-like behavior of rats was tested by weight measurement, open field test, depression preference test, and novelty suppressed feeding test. Long-term potentiation (LTP) was recorded at CA1 synapses in hippocampal slices by electrophysiological method. N-methyl-D-aspartate receptor subunit 2B (NR2B) and calmodulin-dependent protein kinase II (CaMK II) protein levels were examined by using western blot. Results. After the establishment of CUMS-induced depression model, the weight gain rate, sucrose preference rate, line crossing number, and rearing times of rats decreased, and feeding time increased. At the same time, the LTP in hippocampus was impaired, and the expressions of NR2B and CaMK II were upregulated. After EA treatment, the depression-like behavior of rats was improved, the impairment of LTP was reversed, and the expression levels of NR2B and CaMK II protein were downregulated. Conclusion. EA can ameliorate depression-like behaviors by restoring LTP induction, downregulating NR2B and CaMK II expression in CUMS model rats, which might be part of the mechanism of EA antidepressant.

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