scholarly journals Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia

Brain ◽  
2016 ◽  
Vol 139 (3) ◽  
pp. 751-764 ◽  
Author(s):  
Sohail Ejaz ◽  
Julius V. Emmrich ◽  
Sergey L. Sitnikov ◽  
Young T. Hong ◽  
Stephen J. Sawiak ◽  
...  
Keyword(s):  
Brain Damage ◽  
Normobaric Hyperoxia ◽  
Sensorimotor Deficits ◽  
Focal Ischaemia

scholarly journals Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits

Stroke ◽  
2021 ◽  
Author(s):  
Luiz Ricardo C. Vasconcellos ◽  
Letícia Martimiano ◽  
Danillo Pereira Dantas ◽  
Filipe Mota Fonseca ◽  
Hilton Mata-Santos ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Signaling Pathway ◽  
Brain Damage ◽  
Autologous Blood ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Sensorimotor Deficits ◽  
The Brain

Background and Purpose: Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model. Methods: Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls. Results: Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in Nlrp3 knockout mice in comparison to wild-type mice. Conclusions: Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.

scholarly journals Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shi-Yang Ye ◽  
Joanna E. Apple ◽  
Xiao Ren ◽  
Fu-Lei Tang ◽  
Ling-Ling Yao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Brain Damage ◽  
Hippocampal Neurogenesis ◽  
Conditional Knockout ◽  
Microglial Cells ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Sensorimotor Deficits ◽  
Anti Inflammatory

Abstract Background Vacuolar sorting protein 35 (VPS35), a critical component of retromer, is essential for selective endosome-to-Golgi retrieval of membrane proteins. It is highly expressed in microglial cells, in addition to neurons. We have previously demonstrated microglial VPS35’s functions in preventing hippocampal, but not cortical, microglial activation, and in promoting adult hippocampal neurogenesis. However, microglial VPS35’s role in the cortex in response to ischemic stroke remains largely unclear. Methods We used mice with VPS35 cKO (conditional knockout) in microglial cells and examined and compared their responses to ischemic stroke with control mice. The brain damage, cell death, changes in glial cells and gene expression, and sensorimotor deficits were assessed by a combination of immunohistochemical and immunofluorescence staining, RT-PCR, Western blot, and neurological functional behavior tests. Results We found that microglial VPS35 loss results in an increase of anti-inflammatory microglia in mouse cortex after ischemic stroke. The ischemic stroke-induced brain injury phenotypes, including brain damage, neuronal death, and sensorimotor deficits, were all attenuated by microglial VPS35-deficiency. Further analysis of protein expression changes revealed a reduction in CX3CR1 (CX3C chemokine receptor 1) in microglial VPS35-deficient cortex after ischemic stroke, implicating CX3CR1 as a potential cargo of VPS35 in this event. Conclusion Together, these results reveal an unrecognized function of microglial VPS35 in enhancing ischemic brain injury-induced inflammatory microglia, but suppressing the injury-induced anti-inflammatory microglia. Consequently, microglial VPS35 cKO mice exhibit attenuation of ischemic brain injury response.

scholarly journals Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

2011 ◽  
Vol 1 (1) ◽  
pp. 2 ◽  
Author(s):  
Benoit Haelewyn ◽  
Laurent Chazalviel ◽  
Olivier Nicole ◽  
Myriam Lecocq ◽  
Jean-Jacques Risso ◽  
...  
Keyword(s):  
Brain Damage ◽  
Neuronal Degeneration ◽  
Normobaric Hyperoxia

scholarly journals Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia

Brain ◽  
2007 ◽  
Vol 130 (6) ◽  
pp. 1631-1642 ◽  
Author(s):  
Hwa Kyoung Shin ◽  
Andrew K. Dunn ◽  
Phillip B. Jones ◽  
David A. Boas ◽  
Eng H. Lo ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Normobaric Hyperoxia ◽  
Focal Ischaemia
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