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.

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.

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.

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.

Effect of carvedilol on the redox-status of plasma low-molecular-weight aminothyols in rats with acute cerebral ischemia

2018 ◽  
pp. 12-18
Author(s):  
К.А. Никифорова ◽  
В.В. Александрин ◽  
П.О. Булгакова ◽  
А.В. Иванов ◽  
Э.Д. Вирюс ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cerebral Ischemia ◽  
Carotid Arteries ◽  
Redox Status ◽  
Global Cerebral Ischemia ◽  
Low Molecular Weight ◽  
Adrenergic Antagonist ◽  
Acute Cerebral Ischemia ◽  
Common Carotid Arteries ◽  
Reduced Forms

Цель. Установить влияние неспецифического адреноблокатора карведилола на редокс-статус низкомолекулярных аминотиолов (цистеин, гомоцистеин, глутатион) в плазме крови при моделировании глобальной ишемии головного мозга у крыс. Методика. Нами была использована модель глобальной ишемии (пережатие общих сонных артерий с геморрагией длительностью 15 мин). Препарат вводили за 1 ч до операции. Уровни аминотиолов измеряли через 40 мин после начала реперфузии. Анализ уровня аминотиолов проводили методом жидкостной хроматографии. Результаты. Установлено, что у крыс, не подвергавшихся ишемии, карведилол в дозе 10 мг/кг вызывает рост редокс-статуса цистеина и глутатиона (в 3 и 3,5 раза соответственно по сравнению с контролем, p = 0,04 и p = 0,008) за счет увеличения их восстановленных форм. При ишемии данного эффекта не наблюдалось. Редокс-статус у крыс с ишемией на фоне карведилола (Цис = 0,85 ± 0,14%, Глн = 1,8 ± 0,7%, Гцис = 1,1 ± 0,8%) оставался таким же низким, как и у крыс с ишемией без введения карведилола (р > 0,8). Заключение. Полученный результат демонстрирует, что в условиях ишемии головного мозга карведилол не оказывает эффекта на гомеостаз аминотиолов плазмы крови, несмотря на выраженный антиоксидантный эффект в нормальных условиях. Aim. Effect of a nonspecific adrenergic antagonist carvedilol on the redox status of plasma low-molecular-weight aminothiols (cysteine, homocysteine, glutathione) was studied in rats with global cerebral ischemia (occlusion of common carotid arteries with hemorrhage). Methods. A model of global ischemia (occlusion of common carotid arteries with 15-min hemorrhage) was used. The drugs were administered one hour before the operation. Aminothiol levels were measured by HPLC with UV detection at 40 minutes after the onset of reperfusion. Results. Carvedilol 10 mg/kg increased the redox status of cysteine and glutathione in rats not exposed to ischemia (3 and 3.5 times, respectively, compared with the control, p = 0.04 and p = 0.008, respectively) but not of homocysteine, by increasing their reduced forms. However, this effect was not observed in ischemia. In rats with ischemia treated with carvedilol, the redox status (Cys = 0.85 ± 0.14%, GSH = 1.8 ± 0.7%, Hcys = 1.1 ± 0.8%) remained low similar to that in rats with ischemia not treated with carvedilol (p >0.8, 0.8, and 0.9, respectively). Conclusion. Carvedilol did not affect the homeostasis of blood plasma thiols in cerebral ischemia despite the pronounced antioxidant effect under the normal conditions.

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.

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