scholarly journals Intravenous Transplantation of Mesenchymal Stem Cells Reduces the Number of Infiltrated Ly6C+ Cells but Enhances the Proportions Positive for BDNF, TNF-1α, and IL-1β in the Infarct Cortices of dMCAO Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yunqian Guan ◽  
Xiaobo Li ◽  
Wenxiu Yu ◽  
Zhaohui Liang ◽  
Min Huang ◽  
...  
Keyword(s):  
Peripheral Circulation ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Allogeneic Mscs ◽  
Infarct Area ◽  
Infiltrating Cells ◽  
Cerebral Artery Occlusion ◽  
The Brain ◽  
Distal Middle Cerebral Artery

The resident microglial and infiltrating cells from peripheral circulation are involved in the pathological processes of ischemia stroke and may be regulated by mesenchymal stem/stromal cell (MSC) transplantation. The present study is aimed at differentiating the neurotrophic and inflammatory roles played by microglial vs. infiltrating circulation-derived cells in the acute phase in rat ischemic brains and explore the influences of intravenously infused allogeneic MSCs. The ischemic brain injury was induced by distal middle cerebral artery occlusion (dMCAO) in SD rats, with or without MSC infusion in the same day following dMCAO. Circulation-derived infiltrating cells in the brain were identified by Ly6C, a majority of which were monocytes/macrophages. Without MSC transplantation, among the infiltrated Ly6C+ cells, some were positive for BDNF, IL-1β, or TNF-α. Following MSC infusion, the overall number of Ly6C+ infiltrated cells was reduced by 50%. In contrast, the proportions of infiltrated Ly6C+ cells coexpressing BDNF, IL-1β, or TNF-α were significantly enhanced. Interestingly, Ly6C+ cells in the infarct area could produce either neurotrophic factor BDNF or inflammatory cytokines (IL-1β or TNF-α), but not both. This suggests that the Ly6C+ cells may constitute heterogeneous populations which react differentially to the microenvironments in the infarct area. The changes in cellular composition in the infarct area may have contributed to the beneficial effect of MSC transplantation.

scholarly journals Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency

2011 ◽  
Vol 111 (6) ◽  
pp. 1877-1887 ◽  
Author(s):  
Fei Zhou ◽  
Jingchun Guo ◽  
Jieshi Cheng ◽  
Gencheng Wu ◽  
Ying Xia
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Stimulation Parameters ◽  
Cerebral Artery Occlusion ◽  
The Brain

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA.

scholarly journals AMP-Dependent Hypothermia Affords Protection from Ischemic Brain Injury

2012 ◽  
Vol 33 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Mirko Muzzi ◽  
Francesco Blasi ◽  
Alberto Chiarugi
Keyword(s):  
Brain Injury ◽  
Brain Ischemia ◽  
Adenosine Monophosphate ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Stroke Treatment ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Cerebral Artery Occlusion

In light of the relevance of therapeutic hypothermia to stroke treatment, we investigated whether 5′-adenosine monophosphate (AMP)-dependent cooling affords protection from ischemic brain injury. We show that hypothermia by AMP is because of adenosine A1 receptor (A1R) activation and is not invariantly associated with hypotension. Inhibition of ecto-5′-nucleotidase-dependent constitutive degradation of brain extracellular AMP by methylene-ADP (AMPCP) also suffices to prompt A1R-dependent hypothermia without hypotension. Both intraischemic and postischemic hypothermia by AMP or AMPCP reduce infarct volumes and mortality of mice subjected to transient middle cerebral artery occlusion. Data disclose that AMP-dependent hypothermia is of therapeutic relevance to treatment of brain ischemia.

scholarly journals Transient Focal Ischemia Significantly Alters the m 6 A Epitranscriptomic Tagging of RNAs in the Brain

Stroke ◽  
2019 ◽  
Vol 50 (10) ◽  
pp. 2912-2921 ◽  
Author(s):  
Anil K. Chokkalla ◽  
Suresh L. Mehta ◽  
TaeHee Kim ◽  
Bharath Chelluboina ◽  
Jooyong Kim ◽  
...  
Keyword(s):  
Artery Occlusion ◽  
Dot Blot ◽  
Ischemic Brain ◽  
Adverse Conditions ◽  
Functional Implications ◽  
Transient Focal Ischemia ◽  
And Function ◽  
Cerebral Artery Occlusion ◽  
Dot Blot Analysis ◽  
The Brain

Background and Purpose— Adenosine in many types of RNAs can be converted to m 6 A (N 6 -methyladenosine) which is a highly dynamic epitranscriptomic modification that regulates RNA metabolism and function. Of all organs, the brain shows the highest abundance of m 6 A methylation of RNAs. As recent studies showed that m 6 A modification promotes cell survival after adverse conditions, we currently evaluated the effect of stroke on cerebral m 6 A methylation in mRNAs and lncRNAs. Methods— Adult C57BL/6J mice were subjected to transient middle cerebral artery occlusion. In the peri-infarct cortex, m 6 A levels were measured by dot blot analysis, and transcriptome-wide m 6 A changes were profiled using immunoprecipitated methylated RNAs with microarrays (44 122 mRNAs and 12 496 lncRNAs). Gene ontology analysis was conducted to understand the functional implications of m 6 A changes after stroke. Expression of m 6 A writers, readers, and erasers was also estimated in the ischemic brain. Results— Global m 6 A levels increased significantly at 12 hours and 24 hours of reperfusion compared with sham. While 139 transcripts (122 mRNAs and 17 lncRNAs) were hypermethylated, 8 transcripts (5 mRNAs and 3 lncRNAs) were hypomethylated (>5-fold compared with sham) in the ischemic brain at 12 hours reperfusion. Inflammation, apoptosis, and transcriptional regulation are the major biological processes modulated by the poststroke differentially m 6 A methylated mRNAs. The m 6 A writers were unaltered, but the m 6 A eraser (fat mass and obesity-associated protein) decreased significantly after stroke compared with sham. Conclusions— This is the first study to show that stroke alters the cerebral m 6 A epitranscriptome, which might have functional implications in poststroke pathophysiology. Visual Overview— An online visual overview is available for this article.

scholarly journals Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation

2020 ◽  
Vol 21 (20) ◽  
pp. 7668
Author(s):  
Seung-Woo Kim ◽  
Dashdulam Davaanyam ◽  
Song-I Seol ◽  
Hye-Kyung Lee ◽  
Hahnbie Lee ◽  
...  
Keyword(s):  
Adenosine Triphosphate ◽  
Neuronal Damage ◽  
Artery Occlusion ◽  
Brain Parenchyma ◽  
Neutrophil Extracellular Trap ◽  
Dependent Manner ◽  
Peptidylarginine Deiminase ◽  
Ischemic Brain ◽  
Cerebral Artery Occlusion ◽  
The Brain

In ischemic stroke, neutrophils infiltrate damaged brain tissue immediately following the ischemic insult and aggravate inflammation via various mechanisms which include neutrophil extracellular traps (NETs) formation. In the present study, we showed that adenosine triphosphate (ATP), a DAMP molecule, accumulates in the brain and induces NETosis in brain parenchyma and in circulating neutrophils (PMNs) isolated from a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Expression of peptidylarginine deiminase-4 (PAD4), which induces citrullination of histones H3 (CitH3) and initiates NETosis, was significantly enhanced in brain parenchyma and blood PMNs following MCAO. ATP or BzATP (a prototypic P2X7R agonist) significantly enhanced the inductions of PAD4 and CitH3 in a P2X7R-dependent manner and intracellular Ca2+ influx, PKCα activation, and NADPH oxidase-dependent reactive oxygen species (ROS) production play critical roles in this ATP-P2X7R-mediated NETosis. In our MCAO animal model, NETosis was markedly suppressed by treatment with apyrase, an enzyme hydrolyzing ATP, but enhanced by co-treatment of BzATP, confirming ATP-P2X7R-mediated NETosis. Since ATP not only induced NETosis but was also extruded after NETosis, our results indicate that ATP accumulated in the ischemic brain induces NETosis, mediating a cross-talk linking NETosis with neuronal damage that might aggravate inflammation and brain damage.

scholarly journals Adenovirus-Mediated Gene Transfer of Glial Cell Line-Derived Neurotrophic Factor Prevents Ischemic Brain Injury after Transient Middle Cerebral Artery Occlusion in Rats

1999 ◽  
Vol 19 (12) ◽  
pp. 1336-1344 ◽  
Author(s):  
Hisashi Kitagawa ◽  
Chihoko Sasaki ◽  
Kenichi Sakai ◽  
Atsushi Mori ◽  
Yasuhide Mitsumoto ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Brain Injury ◽  
Gene Transfer ◽  
Neurotrophic Factor ◽  
Treated Group ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Gdnf Gene ◽  
Cerebral Artery Occlusion

To examine a possible protective effect of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication-defective adenoviral vector containing GDNF gene (Ad-GDNF) was directly injected into the cerebral cortex at 1 day before 90 minutes of transient middle cerebral artery occlusion (MCAO) in rats. 2,3,5-Triphenyltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-injected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle- or Ad-LacZ-treated group. Enzyme-linked immunosorbent assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene products in the Ad-GDNF-injected group were higher than those of vehicle-treated group at 24 hours after transient MCAO. Immunoreactive GDNF staining was obviously detected in the cortex around the needle track just before or 24 hours after MCAO in the Ad-GDNF group, whereas no or slight GDNF staining was detected in the vehicle group. The numbers of TUNEL, immunoreactive caspase-3, and cytochrome c-positive neurons induced in the ipsilateral cerebral cortex at 24 hours after transient MCAO were markedly reduced by the Ad-GDNF group. These results suggest that the successful exogenous GDNF gene transfer ameliorates ischemic brain injury after transient MCAO in association with the reduction of apoptotic signals.

scholarly journals Iba1+/NG2+ Macrophage-Like Cells Expressing a Variety of Neuroprotective Factors Ameliorate Ischemic Damage of the Brain

2009 ◽  
Vol 30 (3) ◽  
pp. 603-615 ◽  
Author(s):  
Anna Smirkin ◽  
Hiroaki Matsumoto ◽  
Hisaaki Takahashi ◽  
Akihiro Inoue ◽  
Masahiko Tagawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fluorescent Protein ◽  
Artery Occlusion ◽  
Brain Lesions ◽  
Ischemic Lesion ◽  
Ischemic Brain ◽  
Green Fluorescent ◽  
High Level ◽  
Cerebral Artery Occlusion ◽  
The Brain

In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1+/NG2+Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.

Sign in / Sign up

Export Citation Format

Share Document