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 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 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 TNF-α Pretreatment Induces Protective Effects against Focal Cerebral Ischemia in Mice

1997 ◽  
Vol 17 (5) ◽  
pp. 483-490 ◽  
Author(s):  
Hiroshi Nawashiro ◽  
Kaoru Tasaki ◽  
Christl A. Ruetzler ◽  
John M. Hallenbeck
Keyword(s):  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Immunohistochemical Analysis ◽  
Artery Occlusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Ischemic Brain ◽  
Ischemic Episode ◽  
Factor Α ◽  
Cerebral Artery Occlusion

Cytokines are recognized to play an important role in acute stroke. Tumor necrosis factor- α (TNF) is one of the pro-inflammatory cytokines and is expressed in ischemic brain. We hypothesized that TNF might play a role in the regulation of tolerance to ischemia when administered prior to the ischemic episode. We studied the effects of pretreatment of TNF administered intravenously, intraperitoneally, or intracisternally in mice that were subjected to middle cerebral artery occlusion (MCAO) 48 h later. MCAO was performed in BALB/C mice by direct cauterization of distal MCA, which resulted in pure cortical infarction. A significant reduction in infarct size was noted in mice pretreated by TNF at the dose of 0.5 μg/mouse (p < 0.01) intracisternally. At the doses used in this study, administration of TNF by intravenous or intraperitoneal routes was not effective. Immunohistochemical analysis of brains subjected to 24 h of MCAO revealed a significant decrease in CD11b immunoreactivity after TNF pretreatment compared with control MCAO. Preconditioning with TNF affects infarct size in a time- and dose-dependent manner. TNF induces significant protection against ischemic brain injury and is likely to be involved in the signaling pathways that regulate ischemic tolerance.

scholarly journals EphrinB2 activation enhances angiogenesis, reduces amyloid-β deposits and secondary damage in thalamus at the early stage after cortical infarction in hypertensive rats

2018 ◽  
Vol 39 (9) ◽  
pp. 1776-1789 ◽  
Author(s):  
Shihui Xing ◽  
Nannan Pan ◽  
Wei Xu ◽  
Jian Zhang ◽  
Jingjing Li ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Early Stage ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Artery Occlusion ◽  
Advanced Glycation ◽  
Hypertensive Rats ◽  
Secondary Damage ◽  
Function Recovery ◽  
Cerebral Artery Occlusion

Cerebral infarction causes secondary neurodegeneration and angiogenesis in thalamus, which impacts functional recovery after stroke. Here, we hypothesize that activation of ephrinB2 could stimulate angiogenesis and restore the secondary neurodegeneration in thalamus after cerebral infarction. Focal cerebral infarction was induced by middle cerebral artery occlusion (MCAO). Secondary damage, angiogenesis, amyloid-β (Aβ) deposits, levels of ephrinB2 and receptor for advanced glycation end product (RAGE) in the ipsilateral thalamus were determined by immunofluorescence and immunoblot. The contribution of ephrinB2 to angiogenesis was determined by siRNA-mediated knockdown of ephrinB2 and pharmacological activation of ephrinB2. The results showed that formation of new vessels and ephrinB2 expression was markedly increased in the ipsilateral thalamus at seven days after MCAO. EphrinB2 knockdown markedly suppressed angiogenesis coinciding with increased Aβ accumulation, neuronal loss and gliosis in the ipsilateral thalamus. In contrast, clustered EphB2-Fc significantly enhanced angiogenesis, alleviated Aβ accumulation and the secondary thalamic damage, which was accompanied by accelerated function recovery. Additionally, activation of ephrinB2 significantly reduced RAGE levels in the ipsilateral thalamus. Our findings suggest that activation of ephrinB2 promotes angiogenesis, ameliorates Aβ accumulation and the secondary thalamic damage after cerebral infarction. Additionally, RAGE might be involved in Aβ clearance by activating ephrinB2 in the thalamus.

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