scholarly journals Dynamics of pial vessels reactivity after brief cerebral ischemia

2015 ◽  
Vol 14 (1) ◽  
pp. 74-78 ◽  
Author(s):  
O. P. Gorshkova ◽  
M. V. Lensman ◽  
A. I. Artem'eva ◽  
D. P. Dvoretsky
Keyword(s):  
Cerebral Ischemia ◽  
Brain Perfusion ◽  
Artery Occlusion ◽  
Global Cerebral Ischemia ◽  
Pial Arteries ◽  
Pial Vessels ◽  
Transient Global Cerebral Ischemia ◽  
Pial Vessel ◽  
Arteries And Veins

Cerebral blood vessel reactivity is one of the main determinants of final outcome of brain ischemia. Most of studies on the vascular mechanisms of ischemic brain injury, however, focus on the acute changes within ischemic period or several hours after it. Dilatatory capacity of cerebral arterioles (perfusion reservoir) is considered as an important factor of brain perfusion elevation in critical situations.The aim of the present study was to examine the pial vessel reactivity in response to hypercapnia in rats, subjected to transient global cerebral ischemia, at 7, 14 and 21 days after ischemia. Materials and methods. Transient global cerebral ischemia was induced in anesthetized Wistar rats by bilateral common carotid artery occlusion for 12 min with simultaneous controlled hypotension to 45±3 mm Hg, followed by blood reinfusion and recovery from anesthesia. Three different groups of rats were re-anesthetized at 7, 14 or 21 days after ischemia and subjected to microvascular reactivity studies using in vivo video microscopy. Hypercapnia was caused by i.v. injection of acetazolamide. The changes in diameter of pial arteries and veins in response to hypercapnia were measured. Results and discussion. Global cerebral ischemia led to marked decrease in pial vessels (both arteries and veins) reactivity in response to hypercapnia, caused by i.v. injection of acetazolamide. In intact rats, i.v. injection of acetazolamide led to pial arteries dilation and pial veins constriction; in animals subjected to ischemia-reperfuion. the numbers of dilated large arteries and constricted small veins were much less, as well as the extent of arterial dilation. Reactivity changes were observed in all time points studied. Conclusions. Thus, transient global cerebral ischemia cause marked and long lasting (3 weeks) decrease in pial vessel reactivity in response to hypercapnia.

scholarly journals The influence of short-time cerebral ischemia on pial vessels adrenoreactivity in rats

2016 ◽  
Vol 15 (2) ◽  
pp. 73-79
Author(s):  
O. P. Gorshkova ◽  
V. N. Shuvaeva ◽  
M. V. Lensman ◽  
A. I. Artem'eva
Keyword(s):  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Pial Arteries ◽  
Pial Vessels ◽  
Transient Global Cerebral Ischemia ◽  
Brain Surface ◽  
Adrenergic Antagonist ◽  
Microscopy Method ◽  
Short Time

Introduction and purpose. It is known that ischemia influences on endothelial reactions, changes metabolic and myogenic mechanisms of cerebral blood flow regulation. But the role of local neurogenic mechanisms of regulation in change of cerebral vessels reactions after ischemia is finally not found out. The aim of the current study was to examine the pial vessels reactivity in response to a brain surface irrigation by norepinephrine solution in rats, subjected to transient global cerebral ischemia, at 2, 7, 14 and 21 days after ischemia. Materials and methods. Transient global cerebral ischemia was induced in anesthetized Wistar rats by clamping of both common carotid arteries for 12 min with simultaneous controlled hypotension to 45±3 mm Hg, followed by blood reinfusion and recovering from anesthesia. Four different groups of rats were re-anesthetized at 2, 7, 14 or 21 days after ischemia and subjected to microvascular studies using in-vivo video microscopy method. The diameter changes of pial arteries and veins in response to norepinephrine were measured. Results and discussion. It was established that cerebral ischemia led to increase number of the constrictions to norepinephrine mainly at the vessels to relating to group of small pial arteries and arterioles and pial veins of the 3-rd generation. Reactivity changes were observed in all time points studied. This changes probably is connected with caused by ischemia the increase in reactivity and sensitivity of pial vessels adrenoceptors. The greatest changes are noted in 14 days after ischemia. The use of non-selective α-adrenergic antagonist - nicergoline at ischemic and intact rats, led to increase number of the constrictions to norepinephrine. But at ischemic rats decrease was more considerable. And number of dilation reactions to norepinephrine at ischemic rats was also above. It can indicate to increase of adrenoceptors reactivity and sensitivity. Conclusions. Thus, transient global cerebral ischemia cause marked and long lasting (3 weeks) increase in pial vessels reactivity in response to norepinephrine, that is probably connected with increase of adrenoceptors reactivity and sensitivity.

The Antibiotic Erythromycin Induces Tolerance against Transient Global Cerebral Ischemia in Rats (Pharmacologic Preconditioning)

2006 ◽  
Vol 104 (6) ◽  
pp. 1208-1215 ◽  
Author(s):  
Ansgar M. Brambrink ◽  
Ines P. Koerner ◽  
Kathrin Diehl ◽  
Georg Strobel ◽  
Ruediger Noppens ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Messenger Rna ◽  
Neuronal Cell ◽  
Tolerance Induction ◽  
Ischemic Tolerance ◽  
Global Cerebral Ischemia ◽  
Neuroprotective Effects ◽  
Transient Global Cerebral Ischemia ◽  
Cerebral Ischemic

Background Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. Methods Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. Results Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. Conclusions Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

scholarly journals Nadph Oxidase Mediates Striatal Neuronal Injury after Transient Global Cerebral Ischemia

2010 ◽  
Vol 31 (3) ◽  
pp. 868-880 ◽  
Author(s):  
Hideyuki Yoshioka ◽  
Kuniyasu Niizuma ◽  
Masataka Katsu ◽  
Nobuya Okami ◽  
Hiroyuki Sakata ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Late Phase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Global Cerebral Ischemia ◽  
Striatal Neurons ◽  
Reactive Microglia ◽  
Transient Global Cerebral Ischemia

Medium spiny neurons (MSNs) constitute most of the striatal neurons and are known to be vulnerable to ischemia; however, the mechanisms of the vulnerability remain unclear. Activated forms of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase (NOX), which require interaction between cytosolic and membrane-bound subunits, are among the major sources of superoxide in the central nervous system. Although increasing evidence suggests that NOX has important roles in neurodegenerative diseases, its roles in MSN injury after transient global cerebral ischemia (tGCI) have not been elucidated. To clarify this issue, C57BL/6 mice were subjected to tGCI by bilateral common carotid artery occlusion for 22 minutes. Western blot analysis revealed upregulation of NOX subunits and recruitment of cytosolic subunits to the cell membrane at early (3 to 6 hours) and late (72 hours) phases after tGCI. Taken together with immunofluorescent studies, this activation arose in MSNs and endothelial cells at the early phase, and in reactive microglia at the late phase. Pharmacological and genetic inhibition of NOX attenuated oxidative injury, microglial activation, and MSN death after tGCI. These findings suggest that NOX has pivotal roles in MSN injury after tGCI and could be a therapeutic target for brain ischemia.

Induction of Cerebral Ischemic Tolerance by Erythromycin Preconditioning Reprograms the Transcriptional Response to Ischemia and Suppresses Inflammation

2007 ◽  
Vol 106 (3) ◽  
pp. 538-547 ◽  
Author(s):  
Ines P. Koerner ◽  
Matthias Gatting ◽  
Ruediger Noppens ◽  
Oliver Kempski ◽  
Ansgar M. Brambrink
Keyword(s):  
Cerebral Ischemia ◽  
Tolerance Induction ◽  
Transcriptional Response ◽  
Ischemic Tolerance ◽  
Global Cerebral Ischemia ◽  
Regulation Of Transcription ◽  
Complete Suppression ◽  
Expression Array ◽  
Transient Global Cerebral Ischemia

Background A single dose of the macrolide antibiotic erythromycin can induce tolerance against cerebral ischemia in vivo (pharmacologic preconditioning). This study identified potential mechanisms of tolerance induction by assessing effects of erythromycin preconditioning on the cerebral transcriptional response to transient global cerebral ischemia. Methods Preconditioned and nonpreconditioned rats were exposed to 15 min of global cerebral ischemia, and changes in cerebral gene expression were identified by complementary DNA expression array and quantified by real-time reverse-transcription polymerase chain reaction. Results Ischemia caused a widespread up-regulation of transcription in nonpreconditioned brains in this model. Tolerance induction by erythromycin preconditioning reversed this pattern and caused a net down-regulation of a majority of genes, effectively reprogramming the brain's response pattern to ischemia. The most striking change in transcriptional response found in preconditioned animals was an almost complete suppression of the otherwise profound induction of proinflammatory genes by global ischemia. In contrast, the same treatment had little effect on the expression of apoptosis-inducing genes after ischemia. Conclusions These findings present a new molecular correlate for the induction of ischemic tolerance achieved by erythromycin preconditioning and will further the understanding of this clinically important new regimen of preemptive neuroprotection.

Changes in Smad1/5/9 expression and phosphorylation in astrocytes of the rat hippocampus after transient global cerebral ischemia

2021 ◽  
Vol 113 ◽  
pp. 101941
Author(s):  
Takayuki Nakajima ◽  
Yuji Kunieda ◽  
Yusuke Takahashi ◽  
Yuki Tanaka ◽  
Tomohiro Kondo ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Hippocampus ◽  
Global Cerebral Ischemia ◽  
Transient Global Cerebral Ischemia

scholarly journals Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lixuan Zhan ◽  
Xiaomei Lu ◽  
Wensheng Xu ◽  
Weiwen Sun ◽  
En Xu
Keyword(s):  
Plasma Membrane ◽  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Interleukin 1 ◽  
Hypoxic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Free Calcium ◽  
Membrane Translocation ◽  
Vessel Occlusion ◽  
Transient Global Cerebral Ischemia

Abstract Background Our previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI. Methods Transient global cerebral ischemia was induced by the four-vessel occlusion method. Twenty-four hours before ischemia, rats were exposed to systemic hypoxia with 8% O2 for 30 min. Western blotting was used to detect the expression of MLKL and interleukin-1 type 1 receptor (IL-1R1) in CA1. Immunoprecipitation was used to assess the interactions among IL-1R1, RIP3, and phosphorylated MLKL (p-MLKL). The concentration of intracellular free calcium ion (Ca2+) was measured using Fluo-4 AM. Silencing and overexpression studies were used to study the role of p-MLKL in tGCI-induced neuronal death. Results Hypoxic preconditioning decreased the phosphorylation of MLKL both in neurons and microglia of CA1 after tGCI. The knockdown of MLKL with siRNA decreased the expression of p-MLKL and exerted neuroprotective effects after tGCI, whereas treatment with lentiviral delivery of MLKL showed opposite results. Mechanistically, hypoxic preconditioning or MLKL siRNA attenuated the RIP3-p-MLKL interaction, reduced the plasma membrane translocation of p-MLKL, and blocked Ca2+ influx after tGCI. Furthermore, hypoxic preconditioning downregulated the expression of IL-1R1 in CA1 after tGCI. Additionally, neutralizing IL-1R1 with its antagonist disrupted the interaction between IL-1R1 and the necrosome, attenuated the expression and the plasma membrane translocation of p-MLKL, thus alleviating neuronal death after tGCI. Conclusions These data support that the inhibition of MLKL-dependent neuronal necroptosis through downregulating IL-1R1 contributes to neuroprotection of hypoxic preconditioning against tGCI.

scholarly journals LINGO-1 shRNA protects the brain against ischemia/reperfusion injury by inhibiting the activation of NF-κB and JAK2/STAT3

Human Cell ◽  
2021 ◽  
Author(s):  
Jiaying Zhu ◽  
Zhu Zhu ◽  
Yipin Ren ◽  
Yukang Dong ◽  
Yaqi Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Mice Model ◽  
Down Regulation

AbstractLINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, middle cerebral artery occlusion/reperfusion (MACO/R) mice model and HT22 cell oxygen–glucose deprivation/reperfusion (OGD/R) were established to simulate the pathological process of cerebral ischemia in vivo and in vitro and to detect the relevant mechanism. We found that LINGO-1 mRNA and protein were upregulated in mice and cell models. Down-regulation LINGO-1 improved the neurological symptoms and reduced pathological changes and the infarct size of the mice after MACO/R. In addition, LINGO-1 interference alleviated apoptosis and promoted cell proliferation in HT22 of OGD/R. Moreover, down-regulation of LINGO-1 proved to inhibit nuclear translocation of p-NF-κB and reduce the expression level of p-JAK2 and p-STAT3. In conclusion, our data suggest that shLINGO-1 attenuated ischemic injury by negatively regulating NF-KB and JAK2/STAT3 pathways, highlighting a novel therapeutic target for ischemic stroke.

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