scholarly journals Adaptive changes of presynaptic components in hippocampal CA1 subfield after transient global cerebral ischemia

2021 ◽  
Author(s):  
Yan Zhang ◽  
Bai-Hong Tan ◽  
Shuang Wu ◽  
Cheng-Hao Wu ◽  
Jia-Le Suo ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Early Stage ◽  
Ischemia Reperfusion ◽  
Pyramidal Cells ◽  
Global Cerebral Ischemia ◽  
Synapsin I ◽  
Vessel Occlusion ◽  
Transient Global Cerebral Ischemia

Abstract Transient global cerebral ischemia induces acute loss of dendritic spines of CA1 pyramidal neurons in the hippocampus. On the other hand, it is unclear how the presynaptic terminals, which had lost their postsynaptic contacts, are persistently preserved after ischemia. We modeled global cerebral ischemia with two-stage 4-vessel-occlusion in rats, and found that three postsynaptic markers, MAP2, PSD95, and F-actin, were all severely decreased in area CA1 after ischemia/reperfusion (I/R). No significant change was detected for synapsin I, a presynaptic marker, at the protein level in the CA1 region after I/R. However, the puncta size of synapsin I became slightly, but significantly reduced in the early stage of I/R. As time went on, the puncta number of synapsin I became moderately decreased, while the puncta size of synaspin I was significantly increased. Interestingly, some enlarged puncta of synapsin I were observed to terminate directly onto the dendritic shafts of CA1 pyramidal cells. Due to a severe decrease of F-actin in the dendritic spines, the ratio of synapsin I/F-actin puncta number became significantly increased after I/R. The decrease in puncta size of synapsin I in the early stage of I/R may be the result of excessive release of synaptic vesicles due to I/R-induced hyperexcitability in CA3 pyramidal cells, while the increase in puncta size of synapsin I in the later stage of I/R may reflect the disability of synaptic vesicle release due to the loss of postsynaptic contacts.

scholarly journals Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Zahra-Nadia Sharifi ◽  
Farid Abolhassani ◽  
Mohammad Reza Zarrindast ◽  
Shabnam Movassaghi ◽  
Nasrin Rahimian ◽  
...  
Keyword(s):  
Single Dose ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Pyramidal Cells ◽  
Wistar Rat ◽  
Cell Number ◽  
Global Cerebral Ischemia ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Transient Global Cerebral Ischemia

Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6 mg/kg) was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP) 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage.

scholarly journals Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lixuan Zhan ◽  
Xiaomei Lu ◽  
Wensheng Xu ◽  
Weiwen Sun ◽  
En Xu
Keyword(s):  
Plasma Membrane ◽  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Interleukin 1 ◽  
Hypoxic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Free Calcium ◽  
Membrane Translocation ◽  
Vessel Occlusion ◽  
Transient Global Cerebral Ischemia

Abstract Background Our previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI. Methods Transient global cerebral ischemia was induced by the four-vessel occlusion method. Twenty-four hours before ischemia, rats were exposed to systemic hypoxia with 8% O2 for 30 min. Western blotting was used to detect the expression of MLKL and interleukin-1 type 1 receptor (IL-1R1) in CA1. Immunoprecipitation was used to assess the interactions among IL-1R1, RIP3, and phosphorylated MLKL (p-MLKL). The concentration of intracellular free calcium ion (Ca2+) was measured using Fluo-4 AM. Silencing and overexpression studies were used to study the role of p-MLKL in tGCI-induced neuronal death. Results Hypoxic preconditioning decreased the phosphorylation of MLKL both in neurons and microglia of CA1 after tGCI. The knockdown of MLKL with siRNA decreased the expression of p-MLKL and exerted neuroprotective effects after tGCI, whereas treatment with lentiviral delivery of MLKL showed opposite results. Mechanistically, hypoxic preconditioning or MLKL siRNA attenuated the RIP3-p-MLKL interaction, reduced the plasma membrane translocation of p-MLKL, and blocked Ca2+ influx after tGCI. Furthermore, hypoxic preconditioning downregulated the expression of IL-1R1 in CA1 after tGCI. Additionally, neutralizing IL-1R1 with its antagonist disrupted the interaction between IL-1R1 and the necrosome, attenuated the expression and the plasma membrane translocation of p-MLKL, thus alleviating neuronal death after tGCI. Conclusions These data support that the inhibition of MLKL-dependent neuronal necroptosis through downregulating IL-1R1 contributes to neuroprotection of hypoxic preconditioning against tGCI.

Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats

2007 ◽  
Vol 423 (2) ◽  
pp. 162-166 ◽  
Author(s):  
Ignacio González-Burgos ◽  
Graciela Letechipía-Vallejo ◽  
Elisa López-Loeza ◽  
Gabriela Moralí ◽  
Miguel Cervantes
Keyword(s):  
Cerebral Ischemia ◽  
Dendritic Spines ◽  
Pyramidal Cells ◽  
Global Cerebral Ischemia ◽  
Melatonin Treatment ◽  
Term Study ◽  
Ca1 Pyramidal Cells ◽  
Long Term Study ◽  
Hippocampal Ca1

scholarly journals Urinary Proteome Changes in Global Cerebral Ischemia-Reperfusion Injury Rat Model Using Proteomics

2021 ◽  
Author(s):  
Xiaopeng Sun ◽  
Qiujie Li ◽  
Mingshan Wang ◽  
Weiwei Qin
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Early Stage ◽  
Ischemia Reperfusion ◽  
Differentially Expressed ◽  
Global Cerebral Ischemia ◽  
Differentially Expressed Proteins ◽  
Urinary Proteome ◽  
Cerebral Ischemia Reperfusion ◽  
Severe Hypotension

Abstract Background Cerebral ischemia-reperfusion (I/R) injury is the leading cause of death in severe hypotension caused by cardiac arrest, drowning, and excessive blood loss. Urine can sensitively reflect pathophysiological changes in the brain even at an early stage. Methods In this study, a rat model of global cerebral I/R injury was established via Pulsinelli’s four-vessel occlusion (4-VO) method. The proteomics techniques of data-independent acquisition (DIA) and parallel reaction monitoring (PRM) were applied to profile the urinary proteome. The differentially expressed proteins were subjected to Gene Ontology (GO) and protein-protein interaction (PPI) analysis. Results One hundred and sixty-four proteins significantly differed in the 4-VO rat urine samples compared to the control samples (1.5-fold change, p<0.05). GO analysis showed that the acute-phase response, the ERK1 and ERK2 cascade, endopeptidase activity, blood coagulation, and angiogenesis were overrepresented. After PRM validation, fifteen differentially expressed proteins were identified, and their expression was consistent with the DIA quantification. The abundance of FGG, COMP, TFF2, and HG2A was significantly changed only at 12 h after I/R injury. APOE, FAIM3, FZD1, IL1R2, UROK and CD48 were upregulated only at 48 h after I/R injury. KNG1, CATZ, PTGDS, PRVA and HEPC showed an overall trend of upregulation or downregulation at 12 and 48 h after I/R injury, reflecting the progression of cerebral I/R injury. Conclusion In this study, fifteen differentially expressed urinary proteins were identified and validated in a 4-VO rat model. Eight of these proteins were reported to be associated with cerebral I/R injury. These findings provide important clues to inform the monitoring of cerebral I/R injury and further the current understanding of its molecular biological mechanisms.

scholarly journals Functional, Behavioral, and Histological Changes Induced by Transient Global Cerebral Ischemia in Rats: Effects of Cinnarizine and Flunarizine

1989 ◽  
Vol 9 (5) ◽  
pp. 646-654 ◽  
Author(s):  
H. Poignet ◽  
M. Beaughard ◽  
G. Lecoin ◽  
R. Massingham
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Global Cerebral Ischemia ◽  
Experimental Conditions ◽  
Vessel Occlusion ◽  
Transient Global Cerebral Ischemia ◽  
Behavioral Parameters ◽  
Ischemic Episode ◽  
Cerebral Ischemic ◽  
Positive Effect

Temporary cerebral ischemia (15 min) produced by “four-vessel occlusion” in the rat causes neurological disorders, changes in behavior (locomotor hyperactivity), and neuronal damage in the neocortex, striatum, and especially the CA1 zone of the hippocampus. We have studied the effects of two calcium overload blockers, flunarizine (50 mg/kg p.o. twice a day) and cinnarizine (100 mg/kg p.o. twice a day), on these alterations. Cinnarizine markedly improved the functional abnormalities of ischemia but had little or no effect upon the neuronal damage. In contrast, flunarizine provided far greater neuronal protection but with less obvious effects upon behavioral parameters. However, there was evidence of sedation 2 h after treating animals with this dose of flunarizine that might have masked any positive effect of the drug on behavior. We conclude that under the present experimental conditions, there is no correlation between the early and late behavioral changes observed following a temporary cerebral ischemic episode and the histological damage observed in certain vulnerable neurons, particularly in the hippocampus, 72 h after the insult.

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