scholarly journals Combined Genetic Deletion of IL (Interleukin)-4, IL-5, IL-9, and IL-13 Does Not Affect Ischemic Brain Injury in Mice

Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 2207-2215 ◽  
Author(s):  
Carlo Perego ◽  
Stefano Fumagalli ◽  
Kapka Miteva ◽  
Marinos Kallikourdis ◽  
Maria-Grazia De Simoni
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Brain Atrophy ◽  
Ischemic Injury ◽  
Interleukin 4 ◽  
Th2 Cytokines ◽  
Wild Type ◽  
Il Interleukin ◽  
Permanent Occlusion ◽  
Genetic Deletion

Background and Purpose— After ischemic injury, microglia and infiltrated macrophages may acquire different polarization phenotypes promoting inflammation and injury (M1) or repair and protection (M2). There is evidence that immunomodulation, via type 2 helper T-cells (Th2) cytokines, exerts neuroprotection after ischemia. We investigated the consequences of simultaneous genetic deletion of Th2 cytokines (IL [interleukin]-4, IL-5, IL-9, IL-13) on the histopathologic outcome, microglia and infiltrated macrophages markers, and ischemic microenvironment at different time points after ischemic injury in mice subjected to permanent occlusion of the middle cerebral artery. Methods— Wild-type and Th2 cytokine-deficient mice (4KO) were subjected to permanent occlusion of the middle cerebral artery by electrocoagulation and followed up to 5 weeks after permanent occlusion of the middle cerebral artery. Neuropathologic outcome was assessed at 24 hours (n=6), 7 days (n=6), and 5 weeks (n=6–7) by examination of the ischemic lesion, neuronal count, microglia and infiltrated macrophages markers, brain atrophy, collagen deposition, and GFAP (glial fibrillary acidic protein) immunohistochemistry. Selected gene expression was investigated at 7 days (n=6). Results— 4KO mice showed no difference in lesion and neuronal count 7 days and up to 5 weeks after permanent occlusion of the middle cerebral artery compared with wild type. Ischemic 4KO mice had lower CD16/32 expression at 24 hours, lower CD11b and CD16/32 expression at 7 days than wild type. They had higher CD206 expression at 24 hours, higher CD206 and arginase1 at 7 days, and increased mRNA for CXCL9 (chemokine [C-X-C motif] ligand 9) compared with wild type. Additional histopathologic analysis, including brain atrophy, gliotic scar, and collagenous scar confirmed no difference between genotypes at 5 weeks. Conclusions— This study casts light on the proposed neuroprotective function of Th2 cytokines, showing that combined IL-4, IL-5, IL-9, IL-13 deletion does not affect the neuropathologic response to ischemic stroke in the subacute and chronic phases. Our findings indicate that Th2 cytokines are not an essential neuroimmunological cue able to drive the brain’s ischemic outcome.

Abstract 136: Deleterious Effects of Synaptic Zn2+ in a Murine Distal Middle Cerebral Artery Occlusion Model

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Andrew P Carlson ◽  
Lu Li ◽  
Kelsey Thomas ◽  
Christian Sheline ◽  
William Shuttleworth
Keyword(s):  
Stroke Volume ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Wild Type ◽  
Ischemic Brain ◽  
Spreading Depolarization ◽  
Genetic Deletion ◽  
The Right ◽  
Cerebral Artery Occlusion

Background: Previous work has implicated accumulation of Zn2+ as a contributor to ischemic brain injury, however the sources of toxic Zn2+ accumulation are not fully understood. Previous data report that ICV delivery of a Zn2+ chelator limited mild focal stroke (Neuroscience 115 (2002) 871-8). We have recently demonstrated substantial synaptic Zn2+ release following spreading depolarization (JCBFM 31 (2011) 1073-84), and thus it is possible that repetitive spreading depolarization_ known to occur following stroke_ could be a major source of toxic Zn2+. In the present study, we examined whether synaptic Zn2+ release contributes to neuronal injury in a murine focal stroke model. Methods The effect of synaptic Zn2+ was assessed using mice lacking synaptic Zn2+, due to genetic deletion of the synaptic vesicle transporter ZnT3 (ZnT3 KO). Wild type C57Bl/6 mice were age and sex matched as controls. Mice were anesthetized with isofluorane and the cortical branch of the right middle cerebral artery was cauterized via a temporal burrhole. A single surgeon performed the occlusions. Body temperature was maintained at 37±0.5oC during the procedure and recovery. Animals were allowed to recover for 1 week before euthanasia. Stroke volume was assessed by Fluoro-Jade staining. Statistical analysis with 2-way ANOVA was used to determine the effects of sex and genotype on stroke volume. Results: There was no peri- or post-procedural mortality. Infarct was confirmed histologically in all animals. Stroke volume was reduced in the ZnT3 KO mice compared to wild type (mean volume 3.54mm3 versus 8.42mm3 respectively, n=7 for each arm). Only genotype (not sex) had a significant effect on stroke volume by 2-way ANOVA (p=0.0042). Conclusion: Synaptic Zn2+ release leads to increased stroke volume, likely due to toxic Zn2+accumulation. Therapies targeting synaptic release of Zn2+ or repetitive spreading depolarization events (which cause Zn2+ release) may decrease delayed ischemic injuries.

Fetal Cortical Cells Survive in Focal Cerebral Infarct After Permanent Occlusion of the Middle Cerebral Artery in Adult Rats

1992 ◽  
Vol 9 (2) ◽  
pp. 107-112 ◽  
Author(s):  
MOSHE HADANI ◽  
THOMAS FREEMAN ◽  
AMAR MUNSIFF ◽  
WISE YOUNG ◽  
EUGENE FLAMM
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cerebral Infarct ◽  
Cortical Cells ◽  
Adult Rats ◽  
Permanent Occlusion

Post-occlusion treatment with BDNF reduces infarct size in a model of permanent occlusion of the middle cerebral artery in rat

1997 ◽  
Vol 12 (4) ◽  
pp. 271-280 ◽  
Author(s):  
Katsuhiro Yamashita ◽  
Christoph Wiessner ◽  
Dan Lindholm ◽  
Hans Thoenen ◽  
Konstantin-Alexander Hossmann
Keyword(s):  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Permanent Occlusion

Abstract T P82: Long-Term Neurorestorative Effect of α-lipoic Acid Treatment in Focal Cerebral Ischemia Model

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kangho Choi ◽  
Joon-Tae Kim ◽  
Man-Seok Park ◽  
Ki-Hyun Cho
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Lipoic Acid ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Antioxidant Properties ◽  
Ischemic Injury ◽  
Control Group ◽  
Rotarod Test

Introduction: A considerable body of evidence suggests that oxidative stress is a fundamental mechanism of brain damage in stroke. A recent study suggests that the antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no reports of comprehensive studies examining the neurorestorative effects of aLA administered after the onset of ischemia. Hypothesis: The neuroprotective effects of acute treatment with ALA on neuroproliferation and long-term functional recovery following cerebral ischemic injury were examined using an animal model of clinical stroke with middle cerebral artery occlusion (MCAO). Methods: The middle cerebral artery (MCA) of adult male Sprague-Dawley rats was occluded for 2 h and then reperfused. To examine the effect of ALA on brain infarction, ALA (20 mg/kg body weight) was administered after the induction of anesthesia in 71 animals (ALA group) through the left external jugular vein immediately after reperfusion of the left MCAO. An equivalent volume of vehicle was administrated to 71 animals (control group) using the same procedure. A neurologic examination was performed at defined points after MCAO and a neurological deficit score (NDS) was obtained. Motor impairment was assessed by the accelerating rotarod test. Levels of endogenous neural precursor and glial cell were analyzed by immunohistochemistry. Results: Immediate aLA administration group after reperfusion significantly reduced the mortality, infarct size, and NDS than control group (n=71, P=0.005, P=0.002, and P=0.001, respectively). Long-term functional outcomes by Rotarod test were also markedly improved by aLA treatment (P=0.013). After 7 and 14 days of treatment, significantly more cells were labeled with BrdU, nestin, and GFAP in the aLA-treated rats along the infarct and infarct core regions. Significantly more BrdU/GFAP double-labeled cells were observed in the subventricular zone of the aLA group on days 7 and 14. Conclusions: These results indicate that urgent treatment with aLA after ischemic injury may have significant neurorestorative effects through enhanced neuroproliferation. aLA may be a useful intervention for the treatment of acute ischemic stroke.

Arachnoid membrane as a source of sphingosine-1-phosphate that regulates mouse middle cerebral artery tone

2021 ◽  
pp. 0271678X2110333
Author(s):  
Francesc Jiménez-Altayó ◽  
Julia Marzi ◽  
María Galan ◽  
Ana Paula Dantas ◽  
Marisa Ortega ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Arachnoid Membrane ◽  
Sphingosine Kinase 2 ◽  
Basal Tone ◽  
Sphingosine 1 Phosphate ◽  
Genetic Deletion ◽  
In Situ Detection ◽  
Old Mice

Growing evidence indicates that perivascular tissue is critical to modulate vessel function. We hypothesized that the arachnoid membrane surrounding middle cerebral artery (MCA) regulates its function via sphingosine-1-phosphate (S1P)-induced vasoconstriction. The MCA from 3- to 9-month-old male and female wild-type (Oncine France 1 and C57BL/6) mice and sphingosine kinase 2 knockout (SphK2-/-) mice in the C57BL/6 background was mounted in pressure myographs with and without arachnoid membrane. Raman microspectroscopy and imaging were used for in situ detection of S1P. The presence of arachnoid tissue was associated with reduced external and lumen MCA diameters, and with an increase in basal tone regardless of sex and strain background. Strong S1P-positive signals were detected in the arachnoid surrounding the MCA wall in both mice models, as well as in a human post-mortem specimen. Selective S1P receptor 3 antagonist TY 52156 markedly reduced both MCA vasoconstriction induced by exogenous S1P and arachnoid-dependent basal tone increase. Compared to 3-month-old mice, the arachnoid-mediated contractile influence persisted in 9-month-old mice despite a decline in arachnoid S1P deposits. Genetic deletion of SphK2 decreased arachnoid S1P content and vasoconstriction. This is the first experimental evidence that arachnoid membrane regulates the MCA tone mediated by S1P.

Sign in / Sign up

Export Citation Format

Share Document