[D-Ala2, D-Leu5]-Enkephalin (Dadle) Reduces Inflammation Responses after Transient Global Ischemia

2011 ◽  
Vol 345 ◽  
pp. 343-348
Author(s):  
Shu Yan Wang ◽  
Ya Le Duan ◽  
Qing Wen Zeng ◽  
Zheng Zhao ◽  
Xiang Rui Wang
Keyword(s):  
Neuronal Loss ◽  
Brain Regions ◽  
Global Ischemia ◽  
Single Infusion ◽  
Vessel Occlusion ◽  
Ischemic Brain ◽  
Transient Global Ischemia ◽  
Δ Opioid Receptor ◽  
The Right ◽  
Inflammation Responses

[D-Ala2, D-Leu5]-Enkephalin (DADLE) is a δ-opioid receptor antagonist and has been shown to reduce neuronal loss in the selectively vulnerable brain regions after transient global ischemia. Here, we investigate whether this protection is mediated by the DADLE's modulation of the postischemia inflammation responses. After implanted with cannula at the right lateral ventricle, rats underwent 10 minutes of transient global ischemia by four vessel occlusion. Rats received a single infusion of DADLE (12.5 nmol) via the intracerebral cannula at the onset of reperfusion. At the time of 72 h after ischemia, we investigated GFAP expression via immunohistochemistry. we also tested the level of MDA and the activities of SOD and CAT. The results show that DADLE can reduce reactive astrocytosis and increase SOD activities. The study reveals the neuroprotection mechanism of DADLE in the ischemic brain is related to reduce inflammation responses.

Abstract TP83: Stress Exacerbates Global Ischemia-induced Inflammatory Response: Intervention by Progesterone

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Claudia Espinosa-Garcia ◽  
Iqbal Sayeed ◽  
Seema Yousuf ◽  
Fahim Atif ◽  
Elena G Sergeeva ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Therapeutic Potential ◽  
Neuronal Loss ◽  
Global Ischemia ◽  
Male Rats ◽  
Post Injury ◽  
Vessel Occlusion ◽  
Nissl Staining ◽  
Increased Risk ◽  
Factor Expression

Introduction: Stress is associated with increased risk of stroke and poor prognosis, but the mechanisms through which stress may alter stroke outcome remain elusive. Stress compromises neuronal survival and neuroinflammation following an ischemic attack. Post-ischemic inflammatory response involves the activation of microglia, which can be polarized from a harmful M1 phenotype which expresses pro-inflammatory cytokines, to a protective M2 phenotype which releases neurotrophic factors. We hypothesize that progesterone (PROG) will improve global ischemia outcome by modulating microglial polarization in stressed ischemic animals. Methods: Adult male rats were exposed to social defeat stress over 8 consecutive days. Then, rats were subjected to 8 min of global ischemia by the four-vessel occlusion model. PROG (8 mg/Kg/b.w.) was administered by intraperitoneal injection at 2 h post-ischemia followed by subcutaneous injections at 6 h and once every 24 h post-injury for 5 days, and then 2 days with progressively halved dosages. Animals were sacrificed at 7 days post-ischemia. Neuronal loss was assessed by Nissl staining, M1/M2 polarization markers were assessed by immunofluorescence, and pro-inflammatory cytokine and growth factor expression were assessed by western blot. Results: Results revealed extensive neuronal loss and exacerbated microglial activation in hippocampal CA1 region of stressed ischemic rats. Remarkably, both M1 and M2 markers increased. PROG treatment attenuated neuronal loss, robustly reduced M1/M2 markers and significantly increased brain-derived neurotrophic factor expression in the stressed ischemic hippocampus. Conclusion: Our data demonstrate that PROG can modulate neuroinflammation after global ischemic injury by changing microglial phenotype in certain vulnerable brain areas like the hippocampus. These findings support the therapeutic potential of PROG for treating global ischemia with comorbid stress.

scholarly journals Mouse Transient Global Ischemia Two-Vessel Occlusion Model

BIO-PROTOCOL ◽  
2012 ◽  
Vol 2 (18) ◽  
Author(s):  
Fabrizio Pontarelli ◽  
Dimitry Ofengeim ◽  
R. Zukin ◽  
Elizabeth Jonas
Keyword(s):  
Global Ischemia ◽  
Vessel Occlusion ◽  
Occlusion Model ◽  
Transient Global Ischemia

scholarly journals Characterization of BrdU-Positive Neurons Induced by Transient Global Ischemia in Adult Hippocampus

2004 ◽  
Vol 24 (5) ◽  
pp. 548-555 ◽  
Author(s):  
Takayuki Kawai ◽  
Norio Takagi ◽  
Keiko Miyake-Takagi ◽  
Noriko Okuyama ◽  
Nobuyuki Mochizuki ◽  
...  
Keyword(s):  
Global Ischemia ◽  
Vessel Occlusion ◽  
Neuronal Marker ◽  
Helix Loop Helix ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Transient Global Ischemia ◽  
Adult Hippocampus ◽  
Brain Insults

Neurogenesis in the brain continues throughout life and is promoted by brain insults including ischemia. There is no critical conclusion, however, about whether proliferated cells acquire neuronal function after ischemia. Transient global ischemia was produced by a four-vessel occlusion procedure in rats (n = 54). To label proliferative cells, rats were administrated with a single dose of 5-bromo-2’-deoxyuridine (BrdU) at 4, 6, 8, 10, 13, or 15 days after ischemia. Increases in BrdU-positive cells were detected in the hippocampal dentate gyrus at 5, 7, and 9 days after ischemia. To determine the phenotype of BrdU-positive cells, BrdU was administrated twice daily for 3 consecutive days during 6 to 8 days after ischemia. A basic helix–loop–helix transcription factor NeuroD at 7 and 14 days and an immature migrating neuronal marker doublecortin at 14 days after ischemia were expressed transiently in proliferative cells. These proliferative cells after ischemia differentiated to the phenotype of neuron at 28 days after ischemia. Furthermore, BrdU-positive neurons showed phosphorylation of extracellular signal-regulated kinase (ERK) by intracerebroventricular injection of N-methyl-D-aspartate (NMDA) at 28 and 56 days after ischemia as seen in surrounding mature neurons. The number of BrdU-positive neurons, which responded to NMDA stimulation, increased with time after ischemia and was greater than that of sham-operated animals. The present study provides evidence for in vivo ERK phosphorylation in response to NMDA stimulation of BrdU-positive neurons in the adult hippocampus after transient forebrain ischemia.

scholarly journals Effects of ulinastatin on global ischemia via brain pro-inflammation signal

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao-Ming Jiang ◽  
Jing-Hai Hu ◽  
Lu-Lu Wang ◽  
Chi Ma ◽  
Xu Wang ◽  
...  
Keyword(s):  
Brain Regions ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Systemic Injection ◽  
Ca1 Region ◽  
Tissue Edema ◽  
Hippocampal Ca1 ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
Factor Α

AbstractUlinastatin [urinary trypsin inhibitor (UTI)] plays an important role in the protection of organs against ischemic injury during severe inflammation. The purposes of this study were to examine the effects of UTI on the levels of pro-inflammatory cytokines (PICs) and protein expression of PIC receptors in the neocortex and hippocampus CA1 region of rats after transient global ischemia induced via cardiac arrest (CA). Specifcally, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed. CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were employed to determine PICs and their receptors in the neocortex and hippocampus. Our results show that IL-1β, IL-6 and TNF-α were significantly elevated in the neocortex and hippocampal CA1 field after CA. This was accompanied with an increase in PIC receptors, namely IL-1R, IL-6R and TNFR1. Systemic injection of UTI attenuated the amplification of PIC signal pathways in these brain regions. UTI also improved the modified Neurological Severity Score and brain tissue edema in CA rats. Notably, UTI resulted in an increase in survival of CA rats as compared to CA rats without treatment. In conclusion, UTI plays a beneficial role in modulating transient global ischemia induced by CA by altering PIC signal mechanisms, but further studies are needed to draw more firm conclusions.

Neural Underpinnings of Numerical and Spatial Cognition: An fMRI Meta-Analysis of Brain Regions Associated with Symbolic Number, Arithmetic, and Mental Rotation

2019 ◽  
Author(s):  
Zachary Hawes ◽  
H Moriah Sokolowski ◽  
Chuka Bosah Ononye ◽  
Daniel Ansari
Keyword(s):  
Mental Rotation ◽  
Parietal Lobe ◽  
Meta Analysis ◽  
Likelihood Estimation ◽  
Brain Regions ◽  
Angular Gyrus ◽  
Number Representation ◽  
Neural Underpinnings ◽  
The Right ◽  
Symbolic Number

Where and under what conditions do spatial and numerical skills converge and diverge in the brain? To address this question, we conducted a meta-analysis of brain regions associated with basic symbolic number processing, arithmetic, and mental rotation. We used Activation Likelihood Estimation (ALE) to construct quantitative meta-analytic maps synthesizing results from 86 neuroimaging papers (~ 30 studies/cognitive process). All three cognitive processes were found to activate bilateral parietal regions in and around the intraparietal sulcus (IPS); a finding consistent with shared processing accounts. Numerical and arithmetic processing were associated with overlap in the left angular gyrus, whereas mental rotation and arithmetic both showed activity in the middle frontal gyri. These patterns suggest regions of cortex potentially more specialized for symbolic number representation and domain-general mental manipulation, respectively. Additionally, arithmetic was associated with unique activity throughout the fronto-parietal network and mental rotation was associated with unique activity in the right superior parietal lobe. Overall, these results provide new insights into the intersection of numerical and spatial thought in the human brain.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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