scholarly journals Effect of neural stem cell transplantation on cognitive functions of mice after cerebral ischemia-reperfusion

2013 ◽  
Vol 1 (1) ◽  
pp. 92-95 ◽  
Author(s):  
O. Tsupykov ◽  
V. Kyryk ◽  
O. Rybachuk ◽  
P. Poberezhnyi ◽  
A. Mamchur ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cognitive Functions ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Global Cerebral Ischemia ◽  
Ischemic Brain Injury ◽  
Short Term ◽  
Ischemic Brain ◽  
Experimental Animals

This study is aimed to determine the effect of transplantation of neural progenitor cells (NPCs) isolated from fetal hippocampus on cognitive functions of experimental animals after short-term global cerebral ischemia. NPCs were isolated from hippocampus of FVB-Cg-Tg(GFPU)5Nagy/J mice, transgenic by the GFP. Ischemic brain injury in FVB “wild” type mice was modeled by bilateral occlusion of the common carotid arteries for 20 min. GFP-positive NPCs were stereotaxically transplanted into the hippocampus of experimental animals in 24 hours after ischemia-reperfusion. Cognitive functions were evaluated using Morris water maze. Results of this study showed that global short-term cerebral ischemia resulted into cognitive impairments in mice. Stereotaxic transplantation of NPCs promoted the cognitive function recovery in experimental animals after ischemic brain injury. Thus, the data indicates that transplantation of NPCs may have a therapeutic effect in treating of ischemic stroke.

scholarly journals Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia

2015 ◽  
Vol 123 (1) ◽  
pp. 243-253 ◽  
Author(s):  
Yasuo Nishijima ◽  
Kuniyasu Niizuma ◽  
Miki Fujimura ◽  
Yosuke Akamatsu ◽  
Hiroaki Shimizu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Molecular Mechanisms ◽  
Neuronal Injury ◽  
Laser Speckle ◽  
Global Cerebral Ischemia ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Transient Global Cerebral Ischemia

OBJECT Numerous studies have attempted to reveal the pathophysiology of ischemic neuronal injury using a representative transient global cerebral ischemia (tGCI) model in rodents; however, most of them have used gerbil or rat models. Recent advances in transgene and gene-knockout technology have enabled the precise molecular mechanisms of ischemic brain injury to be investigated. Because the predominant species for the study of genetic mutations is the mouse, a representative mouse model of tGCI is of particular importance. However, simple mouse models of tGCI are less reproducible; therefore, a more complex process or longer duration of ischemia, which causes a high mortality rate, has been used in previous tGCI models in mice. In this study, the authors aimed to overcome these problems and attempted to produce consistent unilateral delayed hippocampal CA1 neuronal death in mice. METHODS C57BL/6 mice were subjected to short-term unilateral cerebral ischemia using a 4-mm silicone-coated intraluminal suture to obstruct the origin of the posterior cerebral artery (PCA), and regional cerebral blood flow (rCBF) of the PCA territory was measured using laser speckle flowmetry. The mice were randomly assigned to groups of different ischemic durations and histologically evaluated at different time points after ischemia. The survival rate and neurological score of the group that experienced 15 minutes of ischemia were also evaluated. RESULTS Consistent neuronal death was observed in the medial CA1 subregion 4 days after 15 minutes of ischemia in the group of mice with a reduction in rCBF of < 65% in the PCA territory during ischemia. Morphologically degenerated cells were mostly positive for terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling and cleaved caspase 3 staining 4 days after ischemia. The survival rates of the mice 24 hours (n = 24), 4 days (n = 15), and 7 days (n = 7) after being subjected to 15 minutes of ischemia were 95.8%, 100%, and 100%, respectively, and the mice had slight motor deficits. CONCLUSIONS The authors established a model of delayed unilateral hippocampal neuronal death in C57BL/6 mice by inducing ischemia in the PCA territory using an intraluminal suture method and established inclusion criteria for PCAterritory rCBF monitored by laser speckle flowmetry. This model may be useful for investigating the precise molecular mechanisms of ischemic brain injury.

scholarly journals Influence of exercise training on ischemic brain injury in type 1 diabetic rats

2012 ◽  
Vol 113 (7) ◽  
pp. 1121-1127 ◽  
Author(s):  
Denise M. Arrick ◽  
Hong Sun ◽  
William G. Mayhan
Keyword(s):  
Brain Injury ◽  
Exercise Training ◽  
Vascular Function ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Cerebrovascular Function ◽  
Pial Arterioles

While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50 mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we measured infarct volume in all groups of rats following right MCA occlusion for 2 h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy was performed over the parietal cortex, and we measured responses of pial arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)-dependent, and a NOS-independent agonist in all groups of rats. We found that sedentary diabetic rats had significantly larger total, cortical, and subcortical infarct volumes following ischemia-reperfusion than sedentary nondiabetic, nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS-independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened ischemic brain injury following middle cerebral artery occlusion and restored impaired eNOS- and nNOS-dependent vascular function. Since the incidence of ischemic stroke is increased during T1D, we suggest that our finding are significant in that modest ExT may be a viable preventative therapeutic approach to lessen ischemia-induced brain injury that may occur in T1D subjects.

Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury

1989 ◽  
Vol 256 (2) ◽  
pp. H589-H593 ◽  
Author(s):  
T. H. Liu ◽  
J. S. Beckman ◽  
B. A. Freeman ◽  
E. L. Hogan ◽  
C. Y. Hsu
Keyword(s):  
Hydrogen Peroxide ◽  
Superoxide Dismutase ◽  
Polyethylene Glycol ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Free Radical Scavengers ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.

scholarly journals The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2213
Author(s):  
Ryszard Pluta ◽  
Stanisław J. Czuczwar ◽  
Sławomir Januszewski ◽  
Mirosław Jabłoński
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Disease Type ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
The Brain

Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer’s disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer’s disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer’s disease-type neurodegeneration.

scholarly journals Moderate low temperature protects the ischemic brain injury by activating SIRT1 through inhibition of FOXO1/PINK1/Parkin axis mediated mitophagy in a mouse

2020 ◽  
Author(s):  
Yaobin Zhu ◽  
Yaping Zhang ◽  
Nan Ding ◽  
Hanlu Yi ◽  
Xing Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Low Temperature ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Brain Maturation ◽  
Ischemic Brain Injury ◽  
Biological Functions ◽  
Brain Protection ◽  
Ischemic Brain

Abstract Background: Several evidences suggested that the protective effect of hypothermia on brain injury is related to the inhibition of apoptosis and depends on the onset time of hypothermia and the degree of brain maturation. We performed many experiments aimed to comprehensively explore the biological functions of moderate low temperature protects the ischemic brain injury in a mouse and its underlying mechanism.Methods: 12 normal healthy C57BL6 mouse were selected, and moderate low temperature model mouse were selected. The biological functions of moderate low temperature protect the ischemic brain injury in a mouse and its underlying mechanism were performed to explore.Results: Based on our results, we found that moderate hypothermia brain protection could alleviate cerebral injury caused by ischemia reperfusion in mouse. Hypothermic brain protection reduced the level of oxidative stress induced by ischemia reperfusion in mouse. Meso-hypothermic cerebral protection could inhibit excessive mitochondrial autophagy induced by ischemia reperfusion in mouse. Medium-low temperature brain protection could activate SIRT1 and inhibit FOXO1/PINK1/Parkin pathway. Activation of SIRT1 in the hypoxia/reoxygenation model of hippocampal neurons could inhibit autophagy and oxidative stress by inhibiting the FOXO1/PINK1/Parkin pathway.Conclusions : Moderate low temperature protects the ischemic brain injury by activating SIRT1 through inhibition of FOXO1/PINK1/Parkin axis mediated mitophagy in a mouse.

TIGAR alleviates ischemia/reperfusion-induced autophagy and ischemic brain injury

2019 ◽  
Vol 137 ◽  
pp. 13-23 ◽  
Author(s):  
Ding-Mei Zhang ◽  
Tian Zhang ◽  
Ming-Ming Wang ◽  
Xin-Xin Wang ◽  
Yuan-Yuan Qin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Abstract T MP53: Whole Blood Immuno-Chromatography for Rapid Detection of Cerebral Ischemia in the Pre-Hospital Setting

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Luther C Pettigrew ◽  
Melissa A Bradley-Whitman ◽  
Mark A Lovell
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Whole Blood ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Hospital Setting ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Ischemic Reperfusion ◽  
Arterial Blood

BACKGROUND: Pre-hospital detection of ischemic brain injury will exclude stroke mimics and refine patient triage. Using “dipstick” immuno-chromatography, we validated a rapid-sequence method to identify visinin-like protein-1 (VILIP-1), a neuronal injury marker, in blood sampled after focal cerebral ischemia in rats. METHODS: Transgenic (Tg) rats were constructed to over-express tumor necrosis factor-alpha (TNFα) in brain. Suture-occlusion of the middle cerebral artery (MCAO) was performed in TNFα-Tg animals and wild type (WT) littermates for 1 hr. Arterial blood was sampled at pre-ischemic baseline, after 60 min of MCAO, and at 15 min or 24 hrs of post-ischemic reperfusion. VILIP-1 immuno-reactivity was normalized to pre-ischemic baseline and compared to sham-ischemic animals. Brain infarct volume was measured at 24 hrs. VILIP-1 immuno-reactivity was then correlated with infarct volume to derive Pearson product moment. RESULTS: VILIP-1 immuno-reactivity was increased after 24 hrs of post-ischemic reperfusion in TNFα-Tg animals (133 ± 13 [SD]% of baseline) compared to sham-ischemic rats (100 ± 22; p ≤ 0.05; ANOVA; n = 5 per group). At 15 min (159 ± 36%) and 24 hrs (above), VILIP-1 expression was greater than pre-ischemic baseline ( p ≤ 0.05). Immuno-reactivity of VILIP-1 at 15-min post-ischemic reperfusion was strongly correlated with infarct volume measured at 24 hrs in TNFα-Tg rats (Pearson 0.79; p ≤ 0.01). CONCLUSIONS: Whole blood immuno-chromatography of VILIP-1 is feasible and correlates positively with infarct volume measured at 24 hrs in the rat. These promising results underscore the need to study VILIP-1 immuno-reactivity as an indicator of ischemic brain injury in the pre-hospital setting.

Abstract W P206: Analysis of SUMO3-Modified Proteome in Post-Ischemic Mouse Brain

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Wei Yang ◽  
Huaxin Sheng ◽  
Will Thompson ◽  
Shengli Zhao ◽  
Liangli Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Ischemia Reperfusion ◽  
Global Cerebral Ischemia ◽  
Sham Operation ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
Double Transgenic Mice

Background and Purpose: Small ubiquitin-like modifier (SUMO) conjugation modulates many key cellular processes. Transient cerebral ischemia dramatically activates SUMO2/3 conjugation, and this is believed to be a protective stress response. It is, therefore, of tremendous clinical interest to characterize the SUMO-modified proteome regulated by transient ischemia. We generated a novel SUMO transgenic mouse and performed the first SUMO proteomics study using post-ischemic brain samples. Methods: CAG-loxP-STOP-loxP-SUMO (CAG-SUMO) mice were generated in which His-SUMO1, HA-SUMO2, and FLAG-SUMO3 were expressed from a single multicistronic transgene in a Cre-dependent manner. CAG-SUMO mice were mated with Emx1 Cre/Cre mice to generate double transgenic CAG-SUMO/Emx1-Cre mice as experimental mice and Emx1 Cre/+ mice as control mice. Double transgenic mice were subjected to 10 min global cerebral ischemia followed by 1 h reperfusion or sham operation. FLAG-SUMO3-conjugated proteins were enriched from cortical tissues and analyzed. Results: Characterization of double transgenic mice demonstrated that exogenous expressed tagged SUMO paralogues were functionally intact and did not perturb the endogenous SUMOylation machinery in the brain. FLAG pulldown of cortical samples from sham and ischemia mice followed by GeLC-MS/MS analysis identified 91 candidates whose SUMOylation states were up-regulated in ischemic samples. Data analysis revealed several potentially important processes in which SUMO3 conjugation may play a key role during ischemia/reperfusion, including the cross-talk between SUMOylation and ubiquitination, glucocorticoid receptor signaling, and modulation of posttranscriptional mRNA processing. Conclusions: SUMO proteomic analysis identified important processes and pathways modulated by SUMOylation in the post-ischemic brain that warrant future investigations, since they could be the key to understand the overall impact of SUMOylation on the fate and functions of post-ischemic neurons. The conditional SUMO transgenic mouse will be an invaluable tool for in-depth in vivo analysis of the SUMO-modified proteome in various pathological states.

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