Cross-sectional Area Of Basilar Artery Research Articles

Mechanisms and therapeutic implications of RTA 408, an activator of Nrf2, in subarachnoid hemorrhage-induced delayed cerebral vasospasm and secondary brain injury.

More and more evidence suggests oxidative stress and inflammation contribute importantly to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and secondary brain injury. Recent evidence indicates Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) increases the expression of antioxidant genes and decreases the expression of pro-inflammatory genes. This study examines the effects of an activator of Nfr2, RTA 408, on SAH-induced cerebral vasospasm and possible mechanism underlying its effect in a two-hemorrhage rodent model of SAH. We randomly assigned 60 Sprague-Dawley male rats (350 to 420g) to five groups twelve rats each: one control group (no SAH), one untreated SAH only group and three RTA-408 treatment groups (SAH+ RTA 408 0.5 mg/kg/day, SAH+RTA 408 1 mg/kg/day and a SAH+RTA 408 1.5 mg/kg/day). The treatment groups were administered RTA 408 by intraperitoneal injection thirty min following first induction of SAH for seven days starting with first hemorrhage. Cerebral vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of Nrf2, NF-κB and iNOS in basilar artery and expressions of Nrf2, HO-1, NQO1 and Cleaved caspase-3 were evaluated. Tissue TNF-alpha was assessed by ELISA using the protein sampled from the dentate gyrus, cerebral cortex, and hippocampus. Prior to perfusion fixation, there were no significant physiological differences among the control and treated groups. RTA 408 treatment attenuated the morphological changes caused by cerebral vasospasm. It mitigated SAH-induced suppression of Nrf2 and increased expression of NF-κB and iNOS in the basilar artery. In dentate gyrus, it reversed SAH-decreases in Nrf2, HO-1, NQO-1 and cleaved caspase-3 and RTA 408 1.5 mg/kg/day reversed SAH increases in TNF-alpha. It was concluded that RTA 408 reversal vasospasm was achieved via increases in Nrf2 and decreases in NF-κB and iNOS. It exerted a neuron-protection effect by decreasing the apoptosis-related protein cleaved caspase-3 and decreasing the information cytokine TNF-alpha expression, which it achieved by increasing HO-1 and NQO-1 protein found downstream from Nrf2 and Nrf2. We believe that RTA 408 can potentially be used to manage of cerebral vasospasm and secondary brain injury following SAH.

Application value of phase contrast MR angiography in assessment of the functional posterior communicating artery in patients with posterior circulation ischemia

Objective To investigate the application value of phase contrast MR angiography (PC MRA) in quantitative assessment for the hemodynamic features of functional posterior communicating artery (F-PCoA) in the patients with posterior circulation ischemia (PCI). Methods Data of PC MRA in our Hospital from April 2015 to March 2017 were collected retrospectively. Twenty-six patients (PCI group) were diagnosed as PCI with F-PCoA, and other 25 patients were defined as non-PCI group including 10 patients with F-PCoA (non-PCI group 1) and 15 patients without F-PCoA (non-PCI group 2). The cross-sectional area, mean flux, mean velocity, minimum flux, maximum flux, minimum velocity, and maximum velocity were recorded, and the peak height of flux (maximum flux-minimum flux) and peak height of velocity (maximum velocity - minimum velocity) of basilar artery (BA) were calculated. The subtype, cross-sectional area, mean flux, mean velocity, blood flow direction, and absolute flux of F-PCoA in anterior-posterior direction(sum of both sides)were recorded and analyzed statistically. Results The F-PCoA of 36 cases in PCI group and non-PCI group 1 were divided into three types: type A: the F-PCoA was consistent with anatomical posterior communicating artery (A-PCoA), accounting for 83.3%(30/36 cases); type B: the F-PCoA was not consistent with A-PCoA, accounting for 13.9%(5/36 cases);and type C: a mixed type with the F-PCoA was consistent with A-PCoA in only one side, accounting for 2.8%(1/36 cases). There were no significant differences in the composition of F-PCoA subtype (χ2=0.609, P=0.737) and the absolute flux of F-PCoA in anterior-posterior direction(t=-0.576, P=0.568) between PCI group and non PCI group 1. It could be unidirectional or bidirectional blood flow forasingle F-PCoA during a cardiac cycle. The blood flow direction of bilateral F-PCoA was similar or not in one single case. The obviously main wave peak of the absolute flux curve of F-PCoA in anterior-posterior direction in PCI group were observed. There was a significant difference in the cross-sectional area of BA between non PCI group 1 and 2(t=-2.856, P=0.009), however no significant differences were found in the genders, mean flux, mean velocity, minimum flux, maximum flux, peak height of flux, minimum velocity, maximum velocity, and peak height of velocity of BA. Conclusions PC MRA can be used to quantificationally assess the hemodynamic characteristics of F-PCoA such as flow direction, velocity and flux direction, absolute flux in anterior-posterior direction and morphological changes of F-PCoA, which may provide more information for the PCI diagnosis and treatment. Key words: Brain ischemia; Haemodynamics; Magnetic resonance imaging

Blocking VEGF by Bevacizumab Attenuates VEGF-Induced Vasospasm After Experimental Subarachnoid Hemorrhage in Rabbits

Vasospasm after subarachnoid hemorrhage (SAH) plays a vital role in the development of delayed cerebral ischemia. Anti- vascular endothelial growth factor (VEGF) antibodies, like bevacizumab (BEV), may attenuate VEGF-stimulated angiogenesis, reduced vascular cell proliferation, and improve vasospasm after SAH. Thirty-two adult male New Zealand white rabbits were randomly divided into 4 groups of 8 rabbits in each group: group 1 (control); group 2 (SAH); group 3 (SAH+ vehicle); and group 4 (SAH+ BEV). BEV (5 mg/kg, intraperitoneally) was administered 5 minutes after the intracisternal blood injection and continued for 72 hours once per day in the same dose for group 4. Animals were sacrificed 72 hours after SAH. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups. VEGF is associated with the narrowing of the basilar artery. Treatment with BEV statistically significantly increased the cross-sectional area of the basilar artery when compared with the SAH and the vehicle groups. Basilar artery wall thicknesses in the BEV group was statistically significant smaller than in the SAH and vehicle groups. The hippocampal degeneration scores for the BEV and control groups were similar and significantly lower than those for the SAH and vehicle groups. Cellular proliferation and subsequent vessel wall thickening is a reason to delay cerebral ischemia and deterioration of the neurocognitive function. Intraperitoneal administration of BEV was found to attenuate cerebral vasospasm and prevent delayed cerebral ischemia and improve neurocognitive function after SAH in rabbits.

Hyperglycemia Aggravates Cerebral Vasospasm after Subarachnoid Hemorrhage in a Rat Model.

Hyperglycemia is common and showed to be risky for poor prognosis in patients with subarachnoid hemorrhage (SAH). However, the causality and mechanism underlying this observation are not well established. To investigate the relationship between hyperglycemia and cerebral vasospasm with its pathogenesis in a rat model of SAH. One-shot SAH model was employed in male Sprague-Dawley rats. Hyperglycemia was triggered by intraperitoneal streptozotocin administration (50 mg/kg) 7 days before SAH induction. The severity of cerebral vasospasm was determined by the cross-sectional area of basilar artery (BA) in male rats randomly assigned to 1 of 4 groups: control, hyperglycemia only, SAH only, and SAH with hyperglycemia. The expression of endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) in the BA were analyzed by immunohistochemistry. The mean (standard deviation) blood glucose level was 433.0 (98.3) and 156.5 (31.7) mg/dL in streptozotocin -treated and untreated rats, respectively. Hyperglycemic rats exhibited poorer neurobehavioral performance than normoglycemic rats when subjected to SAH. Hyperglycemia-mediated exacerbation of vasospasm was evident by the greater decrease in the BA cross-sectional area in the hyperglycemic SAH group than in the SAH only group. Furthermore, there was more decreased expression of eNOS and increased expression of iNOS within the vessels of the hyperglycemic SAH rats. Hyperglycemia exacerbated cerebral vasospasm and was associated with poorer neurological outcomes following SAH. Our findings also suggested the nitric oxide pathway as a potential underlying mechanism via the dysregulation of eNOS and iNOS.

The Effect of Intravenous L-Carnitine on the Vasospasm Process in the Experimental Subarachnoid Hemorrhage Model.

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is an important cause of morbidity and mortality. In this study, we examined the effects of L-carnitine on the cerebral vasospasm process. Twenty male New Zealand white rabbits were randomly divided into 4 groups. Group 1 served as control; group 2 was not subjected to SAH and received intravenous L-carnitine 3 times; group 3 was subjected to SAH and group 4 was subjected to SAH and treated with 100 mg/kg intravenous L-carnitine at 0, 24, and 48 hours after SAH. All animals were euthanized by perfusion-fixation 72 hours after SAH induction. The brains were then removed and stored in fixative +4°C overnight. The subjects" basilar arteries were sectioned from four separate zones. Basilar artery cross-sectional areas and thicknesses of vessels were measured by using the SPOT for Windows Version 4.1 computer programme. Statistical comparisons were performed by using the Kruskal-Wallis and Mann-Whitney U tests. Basilar artery wall thicknesses in group 4 were significantly lower than in group 3 (p=0.009). Basilar artery cross-sectional areas in group 4 were higher than in group 3 and the difference was statistically significant (p=0.008). L-carnitine was shown to be potentially beneficial on the resolution of cerebral vasospasm following SAH.

Expression of Sphingosine-1-phosphate (S1P) on the cerebral vasospasm after subarachnoid hemorrhage in rabbits.

To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH). The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9. The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9. Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.

Tanshinone IIA Prevents Rat Basilar Artery Smooth Muscle Cells Proliferation by Inactivation of PDK1 During the Development of Hypertension.

Basilar vascular smooth muscle cells (BASMCs) hyperplasia is a prominent feature of cerebrovascular remodeling and stroke during the development of hypertension. Tanshinone IIA (Tan) has been reported to exhibit a protective effect against the pathological features of hypertension. Previous studies have shown that phosphoinostitide-3 kinase (PI3K)/3'-phosphoinostitide dependent kinase (PDK1)/AKT pathway is involved in the regulation of proliferation of various cell types. Therefore, there may be a crosstalk between Tan antihypertension processes and PI3K/PDK1/AKT proliferative effect in BASMCs. To test this hypothesis, we used a 2-kidney, 2-clip hypertension model to examine the effect of Tan on PI3K/PDK1/AKT pathway by cellular, molecular, and biochemical approaches. Our results revealed that the abundance of PDK1 in plasma was paralleled with an increase in blood pressure and the cross-sectional area of basilar artery in hypertensive rats. Tan decreased blood pressure and hypertension-induced PDK1 phosphorylation but produced no effect on the phosphorylation of PI3K. Moreover, Tan attenuated endothelin 1 induced the activation of PDK1/AKT pathway in rat BASMCs. Tan could inhibit cell cycle transition by regulating the expression of cyclin D1 and p27, in turn, prevent proliferation of BASMCs. Our study provides a novel mechanism by which Tan prevents cerebrovascular cell proliferation during hypertension, and thus Tan may be a potential therapeutic agent for cerebrovascular remodeling and stroke.

Abstract T P244: Correlation between Vasospasm and Microcirculatory Disturbance in Early and delayed Phase following Experimental Subarachnoid Hemorrhage

Background & Objectives: Role of cerebral vasospasm in cerebral microcirculatory disturbance after subarachnoid hemorrhage (SAH) remains to be elucidated. This study investigated the correlation between changes of cerebral microcirculation and time course of arterial narrowing after SAH using rabbit cisterna magna double-blood injection model. Methods: Using 256-multidetector-row computed tomography (CT), CT angiography and CT perfusion were repetitively performed at 0, 1, 6, 24, 48 hours after initial hemorrhage for early changes observation group (ECOG; n=8), and on days 0, 3, 5, 7 for delayed changes observation group (DCOG; n=8). Regional cerebral blood flow (rCBF), cerebral blood volume (CBV), mean transit time (MTT) and mean cross-sectional area of basilar artery (BA) were evaluated at each time point. Results: In ECOG, BA transiently narrowed immediately after SAH and progressively narrowed again after 6 hours. CBV and rCBF were transiently decreased immediately after SAH and restored, and then progressively increased after 6 hours. MTT was transiently prolonged immediately after SAH and gradually restored over 24 hours. In DCOG, basilar arterial narrowing reached a peak on day 5 and improved after day 7. CBV and rCBF were persistently decreased after day 3, while MTT was prolonged after day 5. In both observation groups, there were no significant differences in CTP parameters between in perfusion territory of BA and that of non-BA. Conclusions: Presumably, in this model, delayed cerebral ischemia is caused by the cerebral microcirculatory disturbance which is regulated by independent mechanisms from vasospasm of major arteries both in the early phase and delayed phase following SAH.

Attenuation of cerebral vasospasm and secondary injury by testosterone following experimental subarachnoid hemorrhage in rabbit.

The vasodilatator effects of testosterone have been widely studied and demonstrated. Based on previous studies of these vasodilatatory activities, we hypothesized that testosterone might have potential effects on subarachnoid hemorrhage-induced cerebral vasospasm. Thirty-two adult male New Zealand white rabbits were randomly divided into four groups of eight rabbits in each group: group 1 (control); group 2 (subarachnoid hemorrhage); group 3 (subarachnoid hemorrhage + vehicle); and group 4 (subarachnoid hemorrhage + testosterone). Testosterone (15 mg/kg, intraperitoneally) was administered 5 min after the intracisternal blood injection and continued for 72 h once per day in the same dose for group 4. Animals were killed 72 h after subarachnoid hemorrhage. Basilar artery cross-sectional areas, arterial wall thicknesses, and hippocampal degeneration scores were evaluated in all groups. Intraperitoneal administration of testosterone was found to attenuate cerebral vasospasm and provide neuroprotection after subarachnoid hemorrhage in rabbits. Testosterone treatment was determined to be effective at increasing the luminal area and reducing the wall thickness of the basilar artery. Our findings show that testosterone has some preventive effects on SAH-induced vasospasm and secondary neuronal injury in rabbits. We propose that the vasodilatatory activity of testosterone is due to its effects on inhibiting calcium channels, activating potassium channels, augmenting nitric oxide synthesis, and inhibiting oxidant stress and inflammation.

Role of oxidized LDL and lectin-like oxidized LDL receptor-1 in cerebral vasospasm after subarachnoid hemorrhage.

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication. Free radicals derived from subarachnoid clotting are recognized to play an important role. Oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) have been shown to be related to the pathogenesis of atherosclerosis and may increase in cerebral arteries after SAH, due to the action of free radicals derived from a subarachnoid clot. These molecules may also affect the pathogenesis of vasospasm, generating intracellular reactive oxygen species and downregulating the expression of endothelial NO synthase (eNOS). If so, apple polyphenol might be effective in the prevention of vasospasm due to an abundant content of procyanidins, which exhibit strong radical scavenging effects, and the ability to suppress ox-LDL and LOX-1. The purposes of this study were to investigate changes in levels of ox-LDL and LOX-1 after SAH and whether administering apple polyphenol can modify cerebral vasospasm. Forty Japanese white rabbits were assigned randomly to 4 groups: an SAH group (n = 10); a shamoperation group (n = 10), which underwent intracisternal saline injection; a low-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 10 mg/kg per day from Day 0 to Day 3; and a high-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 50 mg/kg per day. At Day 4, the basilar artery and brain was excised from each rabbit. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar artery, and the expression of ox-LDL, LOX-1, and eNOS was examined for each basilar artery by immunohistochemical staining and reverse transcriptase polymerase chain reaction. In addition, neuronal apoptosis in the cerebral cortex was evaluated by TUNEL. Compared with the sham group, the expression of ox-LDL and LOX-1 in the basilar arterial wall was significantly increased in the SAH group, the expression of eNOS was significantly decreased, and the cross-sectional area of basilar artery was significantly decreased. Compared with the SAH group, the cross-sectional area of basilar artery was increased in the polyphenol groups, together with the decreased expression of ox-LDL and LOX-1 and the increased expression of eNOS. In the high-dose polyphenol group, those changes were statistically significant compared with the SAH group. In the low-dose polyphenol group, those changes were smaller than in the high-dose polyphenol group. No apoptosis and no changes were seen in the cerebral cortex in all groups. This is the first study suggesting that ox-LDL and LOX-1 increase due to SAH and that they may play a role in the pathogenesis of vasospasm. It is assumed that procyanidins in apple polyphenol may inhibit a vicious cycle of ox-LDL, LOX-1, and ROS in a dose-dependent manner. Apple polyphenol is a candidate for preventive treatment of cerebral vasospasm.

The comparative effects of recombinant human erythropoietin and darbepoetin-alpha on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

Darbepoetin alpha is a hypersialylated analogue of erythropoietin effective for activating erythropoietin-receptors. This study investigated the vasodilator and neuroprotective effects of darbepoetin alpha on an experimental subarachnoid hemorrhage model and compared it with erythropoietin. Forty adult male New Zealand white rabbits were randomly divided into four groups of ten rabbits each: group 1 (control), group 2 (subarachnoid hemorrhage), group 3 (erythropoietin), and group 4 (darbepoetin alpha). Recombinant human erythropoietin was administered at a dose of 1,000U/kg intraperitoneally after the induction of subarachnoid hemorrhage and continued every 8h up to 72h. Darbepoetin alpha was administered at a single intraperitoneal dose of 30μg/kg. Animals were killed 72h after subarachnoid hemorrhage. Basilar artery cross-sectional areas, arterial wall thicknesses, hippocampal degeneration scores and biochemical analyses were measured in all groups. Both erythropoietin and darbepoetin alpha treatments were found to attenuate cerebral vasospasm and provide neuroprotection after subarachnoid hemorrhage in rabbits. Darbepoetin alpha revealed better morphometric and histopathological results than erythropoietin among experimental subarachnoid hemorrhage-induced vasospasm. Our findings, for the first time, showed that darbepoetin alpha can prevent vasospasm and provides neuroprotection following experimental subarachnoid hemorrhage. Moreover, darbepoetin alpha showed better results when compared with erythropoietin.

Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.

Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.

Expression of Nemo-Like Kinase (NLK) in the Brain in a Rat Experimental Subarachnoid Hemorrhage Model

This study aimed to investigate the expression of the Nemo-like kinase (NLK) in the brain after experimental subarachnoid hemorrhage (SAH) in rats. A total of 90 rats were randomly divided into six groups: control group, day 1, day 3, day 5, day 7, and day 14. Day 1, day 3, day 5, day 7, and day 14 groups were all SAH groups in which the rats were killed on days 1, 3, 5, 7, and 14, respectively. In SAH groups, autologous arterial blood was injected into cisterna magna once on day 0. Cross-sectional area of basilar artery was measured by H&E staining. Immunostaining and immunoblotting experiments were performed to detect the expression of NLK protein. Real-time polymerase chain reaction was used to analyze the presence and quantity of NLK mRNA. The level of oxidative stress in the artery was also measured. The basilar arteries exhibited vasospasm after SAH and became the most severe on day 3. The expressions of NLK protein and mRNA were decreased remarkably in SAH groups compared with the control group. The down-regulated expression of NLK was detected after SAH and the low ebb was on day 3, which was oppositely the peak time of oxidative stress. The expression of NLK was present mainly in the neurons in the brain and smooth muscle cells in the basilar artery. NLK is decreasingly expressed in an opposite time-course to the development of cerebral vasospasm (CVS) and SAH-induced brain injury in this rat experimental model of SAH and these findings might have important implications during the administration of specific NLK agonist to prevent or reduce CVS or neuronal apoptosis caused by SAH.

The effect of thiocolchicoside on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

This study investigated the effects of thiocolchicoside to prevent cerebral vasospasm in a rabbit model of subarachnoid hemorrhage. Twenty-four adult male New Zealand white rabbits were randomly divided into three groups of eight rabbits each: group 1 (control), group 2 (subarachnoid hemorrhage), group 3 (treatment). Thiocolchicoside (4mg/kg, intraperitoneally) was administered just before intracisternal blood injection and continued for 72h once a day in the same dose for group 3. Animals were killed 72h after subarachnoid hemorrhage. Basilar artery cross-sectional areas and arterial wall thicknesses were measured in all groups. Intraperitoneal administration of thiocolchicoside was found to attenuate cerebral vasospasm after subarachnoid hemorrhage in rabbits. Thiocolchicoside treatment was determined to be effective in increasing the luminal area and reducing the wall thickness of the basilar artery. Our findings, for the first time, showed that TCC can prevent vasospasm induced by SAH. Our results also showed that GABAergic activity may play an important role in cerebral vasospasm etiopathogenesis. In conclusion, the thiocolchicoside treatment might be beneficial in preventing vasospasm after subarachnoid hemorrhage, thus showing potential for clinical application.

Effects of Intramuscular Parecoxib Administration on Vasospasm in an Experimental Subarachnoid Hemorrhage Model

ABSTRACTAim: We examined whether intramuscular parecoxib administration has a preventive or therapeutic effect on vasospasm following experimental subarachnoid hemorrhage (SAH). Materials and Methods: Twenty New Zealand White Rabbits were assigned randomly to one of four groups. Animals in Group I were not subjected to SAH (control group). Animals in all other groups were subjected to SAH. Animals in Group II received no treatment after SAH induction (SAH group). Animals in Group III received intramuscular parecoxib (diluted with saline) injection at 6 and at 30 hours after SAH (treatment group). Animals in Group IV received only intramuscular saline injection at 6 and at 30 hours after SAH (vehicle group). Animals were euthanized by perfusion and fixation 48 hours after SAH induction. Basilar artery cross-sectional areas and wall thicknesses were measured. Statistical comparisons were performed using Kruskal–Wallis and Mann–Whitney U tests. Results: Basilar artery cross-sectional areas in the treatment group were significantly higher than in the SAH or vehicle group (p < .05). Basilar artery wall thickness in the treatment group was significantly smaller than in the SAH or vehicle group (p < .05). Conclusion: Our study revealed that intramuscular administration of parecoxib significantly attenuates vasospasm following experimental SAH.

Expression of CD137 in the cerebral artery after experimental subarachnoid hemorrhage in rats: A pilot study

Inflammation and immunity play a crucial role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). CD137 is recognized as an independent costimulatory molecule of T cells and activator of monocytes. A growing body of evidence indicates that CD137 is vital for inflammation and immunity. Therefore, this study aimed to investigate the expression of CD137 in the basilar artery in a rat SAH model and to clarify the potential role of CD137 in cerebral vasospasm. A total of 107 rats were randomly divided into four groups: control group; day 3, day 5, and day 7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in SAH groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were sacrificed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the CD137 expression was assessed by quantitative real-time PCR, Western blot and immunohistochemistry. The cross-sectional area of basilar artery was found to be 57,944 ± 5581 μm 2 in control group, 26,100 ± 2639 μm 2 in day 3, 19,723 ± 2412 μm 2 in day 5, and 28,800 ± 2980 μm 2 in day 7 group, respectively. The basilar artery exhibited vasospasm after SAH and became more severe on day 5. The elevated mRNA and protein of CD137 were detected after SAH and peaked on day 5. CD137 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH. These findings indicate the possible role of CD137 in the pathogenesis of cerebral vasospasm after SAH.

Expression of NF-E2-related factor 2 (Nrf2) in the basilar artery after experimental subarachnoid hemorrhage in rabbits: A preliminary study

It has been suggested that the pathogenesis of vasospasm is complex including endothelial damage, oxidative stress, inflammatory damage, and the accumulation of toxic metabolites. Recently, a growing body of evidence indicates that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. In this study, a total of 48 rabbits were assigned randomly to four groups: control group, SAH day 3, day 5, and day 7 groups. The animals in SAH day 3, day 5, and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the Nrf2 expression was assessed by immunohistochemistry and Western blot analysis. The mRNA levels of Nrf2 were also determined by RT–PCR. The basilar arteries exhibited vasospasm after SAH and became more severe on days 3 and 5. The elevated expression of Nrf2 was detected after SAH and peaked on days 3 and 5. Nrf2 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rabbit experimental model of SAH.

N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage

Background This study investigated the ability of NAC to prevent cerebral vasospasm in a rabbit model of SAH. Methods Twenty-one, male New Zealand white rabbits were randomly divided into 3 groups of 7 rabbits each: group 1 (control), group 2 (SAH only), group 3 (SAH + NAC treatment). NAC (150 mg/kg, single dose, IP) was administered just before SAH and continued until 72 hours after SAH in group 3. Animals were killed 72 hours after SAH. Tissue MDA levels, SOD, and GSH-Px activities were measured, and basilar artery cross-sectional areas, arterial wall thickness, and endothelial apoptosis in a cross section of basillary artery were determined in all groups. Results Intraperitoneal administration of NAC was found to be markedly effective against developing a cerebral vasospasm following a SAH in rabbits. It could significantly reduce elevated lipid peroxidation and increase the level of tissue GSH-Px and SOD enzymatic activities. Also, NAC treatment was found to be effective in increasing the luminal area and reducing wall thickness of the basilar artery. The morphology of arteries in the NAC treatment group was well protected. NAC markedly reduced apoptotic index and protects the endothelial integrity. Conclusions This study demonstrates, for the first time, that NAC treatment attenuates cerebral vasospasm in a rabbit SAH model. NAC treatment has significant neuroprotective effect and markedly prevents cerebral vasospasm after SAH. In conclusion, the NAC treatment might be beneficial in preventing cerebral vasospasm after SAH, thus showing potential for clinical implications.

Expression of monocyte chemoattractant protein-1 in the cerebral artery after experimental subarachnoid hemorrhage

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated that MCP-1 has been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and others in the central nervous system, the role of MCP-1 in the cerebral artery after experimental subarachnoid hemorrhage (SAH) in rats has been largely unexplored. This study was undertaken to investigate the expression of the MCP-1 in SAH model and to clarify the potential role of MCP-1 in cerebral vasospasm. A total of 80 rats were randomly divided into four groups: control group; day 3, day 5, and day 7 groups. Day 3, day 5, and day 7 groups were all SAH groups. The animals in day 3, day 5 and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the MCP-1 expression was assessed by real-time PCR, Western blot and immunohistochemistry. The cross-sectional area of basilar artery was found to be 85,373 ± 8794 μm 2 in control group, 59,210 ± 7281 μm 2 in day 3, 50,536 ± 6519 μm 2 in day 5, and 66,360 ± 7452 μm 2 in day 7, respectively. The basilar arteries exhibited vasospasm after SAH and became more severe on day 5. The elevated mRNA and protein of MCP-1 were detected after SAH and peaked on day 5. MCP-1 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rat experimental model of SAH and these findings might have important implications during the administration of specific MCP-1 antagonists in order to prevent or reduce cerebral vasospasm caused by SAH.

Effects of raloxifene on cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits

Background The aim of this study was to investigate the ability of a SERM, RLX, to prevent vasospasm in a rabbit model of SAH. Methods Thirty-four New Zealand white rabbits were allocated into 3 groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH [n = 12]), (2) SAH only (n = 12), and (3) SAH plus RLX (n = 10). Basilar artery lumen areas and arterial wall thickness were measured to assess vasospams in all groups. Results There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups ( P < .05). The difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements in the RLX-treated group was statistically significant ( P < .05). The difference between the SAH group and the SAH + RLX group was also statistically significant ( P < .05). Conclusions These findings demonstrate that RLX has marked vasodilatatory effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this SERM drug could be used as possible anti-vasospastic agent in patients without major adverse effects.