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.

scholarly journals Exercise training normalizes impaired NOS-dependent responses of cerebral arterioles in type 1 diabetic rats

2011 ◽  
Vol 300 (3) ◽  
pp. H1013-H1020 ◽  
Author(s):  
William G. Mayhan ◽  
Denise M. Arrick ◽  
Kaushik P. Patel ◽  
Hong Sun
Keyword(s):  
Exercise Training ◽  
Brain Tissue ◽  
Diabetic Rats ◽  
Protein Levels ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Enos Protein

Our goal was to examine whether exercise training (ExT) could normalize impaired nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during type 1 diabetes (T1D). We measured the in vivo diameter of pial arterioles in sedentary and exercised nondiabetic and diabetic rats in response to an endothelial NOS (eNOS)-dependent (ADP), an neuronal NOS (nNOS)-dependent [ N-methyl-d-aspartate (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we measured superoxide anion levels in brain tissue under basal conditions in sedentary and exercised nondiabetic and diabetic rats. Furthermore, we used Western blot analysis to determine eNOS and nNOS protein levels in cerebral vessels/brain tissue in sedentary and exercised nondiabetic and diabetic rats. We found that ADP and NMDA produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic rats. In contrast, ADP and NMDA produced only minimal vasodilation in sedentary diabetic rats. ExT restored impaired ADP- and NMDA-induced vasodilation observed in diabetic rats to that observed in nondiabetics. Nitroglycerin produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic and diabetic rats. Superoxide levels in cortex tissue were similar in sedentary and exercised nondiabetic rats, were increased in sedentary diabetic rats, and were normalized by ExT in diabetic rats. Finally, we found that eNOS protein was increased in diabetic rats and further increased by ExT and that nNOS protein was not influenced by T1D but was increased by ExT. We conclude that ExT can alleviate impaired eNOS- and nNOS-dependent responses of pial arterioles during T1D.

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

scholarly journals Interleukin-1β Transfer across the Blood–Brain Barrier in the Ovine Fetus

2015 ◽  
Vol 35 (9) ◽  
pp. 1388-1395 ◽  
Author(s):  
Grazyna B Sadowska ◽  
Xiaodi Chen ◽  
Jiyong Zhang ◽  
Yow-Pin Lim ◽  
Erin E Cummings ◽  
...  
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Brain Regions ◽  
Interleukin 1Β ◽  
Brain Barrier ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Blood Brain ◽  
Hypoxic Ischemic Brain Injury

Pro-inflammatory cytokines contribute to hypoxic–ischemic brain injury. Blood–brain barrier (BBB) dysfunction represents an important component of hypoxic–ischemic brain injury in the fetus. Hypoxic–ischemic injury could accentuate systemic cytokine transfer across the fetal BBB. There has been considerable conjecture suggesting that systemic cytokines could cross the BBB during the perinatal period. Nonetheless, evidence to support this contention is sparse. We hypothesized that ischemia–reperfusion increases the transfer of systemic interleukin-1β (IL-1β) across the BBB in the fetus. Ovine fetuses at 127 days of gestation were studied 4 hours after 30 minutes of bilateral carotid artery occlusion and compared with a nonischemic group. Recombinant ovine IL-1β protein was expressed from an IL-1β pGEX-2 T vector in E. coli BL-21 cells and purified. The BBB function was quantified in 12 brain regions using a blood-to-brain transfer constant with intravenous 125I-radiolabeled IL-1β (125I-IL-1β). Interleukin-1β crossed the intact BBB in nonischemic fetuses. Blood-to-brain transport of 125I-IL-1β was higher ( P < 0.05) across brain regions in fetuses exposed to ischemia–reperfusion than nonischemic fetuses. We conclude that systemic IL-1β crosses the intact fetal BBB, and that ischemia–reperfusion increases transfer of this cytokine across the fetal BBB. Therefore, altered BBB function after hypoxia–ischemia facilitates entry of systemic cytokines into the brain of the fetus.

scholarly journals Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetesThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (8) ◽  
pp. 788-795 ◽  
Author(s):  
Weiguo Li ◽  
Aisha I. Kelly-Cobbs ◽  
Erin M. Mezzetti ◽  
Susan C. Fagan ◽  
Adviye Ergul
Keyword(s):  
Brain Injury ◽  
Cerebral Perfusion ◽  
Infarct Volume ◽  
Cerebral Arteries ◽  
Age Groups ◽  
Diabetic Rats ◽  
Ischemic Brain Injury ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
Neurovascular Damage

Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood–brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto–Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.

scholarly journals Effect of 3-Aminobenzamide on the Ultrastructure of Astrocytes and Microvessels After Focal Cerebral Ischemia in Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581990124 ◽  
Author(s):  
Jinqiao Wang ◽  
Chunyan Ma ◽  
Jing Zhu ◽  
Gaofeng Rao ◽  
Hongjuan Li
Keyword(s):  
Brain Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Parp Inhibition ◽  
Ultrastructural Changes ◽  
Critical Event ◽  
Ischemic Brain Injury ◽  
Sprague Dawley ◽  
Ischemic Brain ◽  
Perivascular Edema

The disruption of blood–brain barrier (BBB) is a critical event in the formation of brain edema during early phases of ischemic brain injury. Poly(ADP-ribose) polymerase (PARP) activation, which contributes to BBB damage, has been reported in ischemia–reperfusion and traumatic brain injury. Here, we investigated the effect of 3-aminobenzamide (3-AB), a PARP-1 inhibitor, on the ultrastructure of BBB. Male Sprague Dawley rats were suffered from 90 minutes of middle cerebral artery occlusion, followed by 4.5 hours or 22.5 hours of reperfusion (R). The vehicle or 3-AB (10 mg/kg) was administered intraperitoneally (ip) 60 minutes after lacking of blood. Tissue Evans Blue (EB) levels, ultrastructures of astrocytes and microvessels, and areas of perivascular edema were examined in penumbra and core, at I 1.5 hours /R 4.5 hours and I 1.5 hours /R 22.5 hours, respectively. The severity of ultrastructural changes was graded with a scoring system in each group. We showed that 3-AB treatment significantly decreased tissue EB levels and ultrastructural scores, attenuated damages in astrocytes and microvessels, and reduced areas of perivascular edema. In conclusion, PARP inhibition may provide a novel therapeutic approach to ischemic brain injury.

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.

Abstract W P220: Suppression of Interleukin 33 Limits Ischemic Brain Injury and Improves Functional Outcome in Murine Stroke Model

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Atif Zafar ◽  
Mohammad M Khan ◽  
Asgar Zaheer
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Functional Outcome ◽  
Ischemia Reperfusion ◽  
Neutralizing Antibody ◽  
Neurological Deficits ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Interleukin 33 ◽  
The Brain

Background and purpose: Ischemic stroke is a leading cause of death and disability worldwide, and the treatment options are limited. Interleukin-33 (IL-33) is a newly recognized IL-1 family cytokine which signals via its ST2 receptor, and acts as a key regulator of inflammation. However, the expression of IL-33 in the brain was not well studied and its expression in ischemic stroke remains to be elucidated. In the present study, we measured IL-33 and ST2 levels and examine the correlation of IL-33 expression with brain damage and functional outcome following ischemic stroke. Methods: IL-33 expression was examined in ischemic brain hemisphere. Mice were subjected to middle cerebral artery occlusion (MCAO) for 1 hr using a filament model, followed by 23 hrs reperfusion. Briefly, mice were anesthetized with 1-1.5% isoflurane mixed with medical oxygen. Body temperature was maintained at 37°C ± 1.0 using a heating pad. At 23 hours after ischemia/reperfusion, mice were tested for neurological scores and were sacrificed for the estimation of IL-33 and ST2 expression. Expression of IL-33 and its receptor ST2 was monitored by ELISA, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, expression of NF-kB and proinflammatory cytokines were evaluated after ischemia/reperfusion. Results: We found significantly increased expression level of IL-33 and ST2 in the MCAO mice as compare to the saline treated control mice. Moreover, treating the MCAO mice with recombinant IL-33 increases the brain injury and worsens neurological deficits in MCAO mice as compare to control mice. Interestingly, increased ischemic brain damage and neurological deficits were largely abrogated in mice treated with IL-33 neutralizing antibody. Conclusion: These findings provide the first evidence that IL-33/ST2 signaling plays an important role in the pathogenesis of stroke. Moreover, IL-33 exacerbates inflammatory brain injury after ischemic stroke and treatment with specific IL-33 neutralizing antibody inhibited the ischemic brain injury. Therefore, blocking the IL-33 may represent an efficient therapy in stroke.

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