Prevention of cerebral vasospasm by local delivery of cromakalim with a biodegradable controlled-release system in a rat model of subarachnoid hemorrhage

2009 ◽  
Vol 110 (5) ◽  
pp. 1015-1020 ◽  
Author(s):  
Ibrahim Omeis ◽  
Weiliam Chen ◽  
Meena Jhanwar-Uniyal ◽  
Renato Rozental ◽  
Raj Murali ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Controlled Release ◽  
Cerebral Vasospasm ◽  
Rat Model ◽  
Smooth Muscles ◽  
Dependent Manner ◽  
Release System ◽  
Basilar Arteries ◽  
Controlled Release System ◽  
Dose Dependent

Object One mechanism that contributes to cerebral vasospasm is the impairment of potassium channels in vascular smooth muscles. Adenosine triphosphate–sensitive potassium channel openers (PCOs) appear to be particularly effective for dilating cerebral arteries in experimental models of subarachnoid hemorrhage (SAH). A mode of safe administration that provides timed release of PCO drugs is still a subject of investigation. The authors tested the efficacy of locally delivered intrathecal cromakalim, a PCO, incorporated into a controlled-release system to prevent cerebral vasospasm in a rat model of SAH. Methods Cromakalim was coupled to a viscous carrier, hyaluronan, 15% by weight. In vitro release kinetics studies showed a steady release of cromakalim over days. Fifty adult male Sprague-Dawley rats weighing 350–400 g each were divided into 10 groups and treated with various doses of cromakalim or cromakalim/hyaluronan in a rat double SAH model. Treatment was started 30 minutes after the second SAH induction. Animals were killed 3 days after treatment, and the basilar arteries were processed for morphometric measurements and histological analysis. Results Controlled release of cromakalim from the cromakalim/hyaluronan implant at a dose of 0.055 mg/kg significantly increased lumen patency in a dose-dependent manner up to 94 ± 8% (mean ± standard error of the mean) of the basilar arteries of the sham group compared with the empty polymer group (p = 0.006). Results in the empty polymer group were not different from those in the SAH-only group, with a lumen patency of 65 ± 12%. Lumen patencies of the cromakalim-only groups did not differ in statistical significance at low (64 ± 9%) or high (66 ± 7%) doses compared to the SAH-only group. Conclusions Treatment of SAH with a controlled-release cromakalim/hyaluronan implant prevented experimental cerebral vasospasm in this rat double hemorrhage model; this inhibition was dose-dependent. The authors' results confirm that sustained delivery of cromakalim perivascularly to cerebral vessels could be an effective therapeutic strategy in the treatment of cerebral vasospasm after SAH.

Oral administration of an inhibitor of endothelin-converting enzyme attenuates cerebral vasospasm following experimental subarachnoid haemorrhage in rabbits

2002 ◽  
Vol 103 (s2002) ◽  
pp. 414S-417S ◽  
Author(s):  
Aij-Lie KWAN ◽  
Chih-Lung LIN ◽  
Chih-Zen CHANG ◽  
Daniel WINARDI ◽  
Chun-Po YEN ◽  
...  
Keyword(s):  
Subarachnoid Haemorrhage ◽  
Oral Administration ◽  
Cerebral Vasospasm ◽  
Statistical Significance ◽  
Autologous Blood ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Endothelin Converting Enzyme ◽  
Basilar Arteries ◽  
Dose Dependent

Increasing evidence has implicated endothelin-1 (ET-1), a potent vasoconstrictive peptide, in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage (SAH). Endothelin-converting enzyme-1 (ECE-1), the protease involved in the final step of post-translational processing of ET-1, cleaves the inactive precursor big ET-1 at the Trp21–Val 22 peptide bond. In our previous study, we found that an inhibitor of ECE-1, CGS 26303, could prevent and reverse the arterial narrowing after SAH in rabbits. CGS 26393, a prodrug of CGS 26303, is an orally active, long-acting inhibitor of ECE-1. The present study examined the effects of CGS 26393 on the prevention and reversal of cerebral vasospasm after SAH. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. In the prevention study, the drug was given orally 1h before the induction of SAH. All drug treatments in the reversal study were initiated at 23h after induction of SAH. One of three dosages (3, 10 or 30mg/kg) of CGS 26393 or vehicle was administrated orally twice daily, and all animals were sacrificed by perfusion and fixation 48h after SAH. Basilar arteries were removed and sectioned, and cross-sectional areas were measured. Cerebrospinal fluid (CSF) was collected prior to perfusion. Oral administration of CGS 26393 attenuated SAH-induced cerebral vasospasm in a dose-dependent manner in both the prevention and reversal groups. These effects achieved statistical significance at all dosages when compared with the SAH-only or SAH plus vehicle groups. Moreover, the attenuation of vasospasm following oral administration of CGS 26393 was more efficacious than that obtained with bolus injections of CGS 26303. The levels of free CGS 26303 in the CSF were increased in a dose-dependent manner in all three CGS 26393-treated groups. This study provides the first evidence that oral administration of an inhibitor of ECE-1, CGS 26393, is capable of preventing and reversing cerebral vasospasm following SAH. These findings also reinforce evidence demonstrating that treatment with an ECE-1 inhibitor is a potentially viable therapeutic approach for reducing cerebral vasospasm after SAH.

scholarly journals APC Overexpression Suppresses the Pyroptosis of Subarachnoid Hemorrhage Model Cells through Regulating NLRP3 Inflammasome Pathway

2021 ◽  
Author(s):  
Ai Yan ◽  
Xuyan Pan ◽  
Xianqiang Wen ◽  
Xiaohu Nie ◽  
Yuntao Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Activated Protein C ◽  
Dependent Manner ◽  
Balance Beam ◽  
Novel Strategy ◽  
Dose Dependent

Abstract Subarachnoid hemorrhage (SAH) is a kind of hemorrhagic stroke with high mortality. Activated protein C (APC) was implicated to play a neuroprotective role in central nervous system diseases. However, its role in SAH remains unclear. Our study aims to investigate the role of APC and its regulatory mechanism in SAH. The SAH rat model was constructed by internal carotid artery puncture. The SAH cell model was established by the application of oxygen hemoglobin. ELISA was performed to detect the level of cytokines. Flow cytometry was used to detect the population of pyroptosis cells. Neurological functions of rats were estimated using modified Garcia scoring and balance beam test. SAH hemorrhage was estimated using modified Sugawara's scoring. APC was significantly increased and NLRP3 was decreased in SAH rat model in a time-dependent manner. The application of APC recombinant protein 3K3A-APC could notably ameliorate SAH hemorrhage and improve neurological functions. Besides, 3K3A-APC could inhibit pyroptosis in a dose-dependent manner in SAH cell model. Moreover, the inhibition of NLRP3 could reverse the effects induced by the knockdown of APC. Our study revealed that APC could ameliorate SAH-induced EBI by suppressing pyroptosis via inhibiting NLRP3 inflammasome, which would provide a novel strategy for the treatment of SAH.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Microorganism-based monodisperse microcapsules: encapsulation of the fungicide tebuconazole and its controlled release properties

RSC Advances ◽  
2015 ◽  
Vol 5 (32) ◽  
pp. 25164-25170 ◽  
Author(s):  
Bo Zhang ◽  
Teng Zhang ◽  
Quanxi Wang ◽  
Tianrui Ren
Keyword(s):  
Controlled Release ◽  
Powdery Mildew ◽  
Drug Release ◽  
Release Rate ◽  
Drug Release Rate ◽  
Burst Effect ◽  
Initial Burst ◽  
Release System ◽  
Controlled Release System ◽  
Monodisperse Microcapsules

A controlled release system was prepared, it based on UF modified PCC cells in which TEB are loaded into cells. It can control the drug release rate, depress the initial “burst effect”, and was efficacious in controlling wheat powdery mildew.

Safflower injection inhibits pulmonary arterial remodeling in a monocrotaline-induced pulmonary arterial hypertension rat model

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Aifeng Chen ◽  
Shibiao Ding ◽  
Liangliang Kong ◽  
Jianpu Xu ◽  
Fei He ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Cardiac Muscle ◽  
Rat Model ◽  
Dependent Manner ◽  
Arterial Remodeling ◽  
Pulmonary Arterial ◽  
Dose Dependent

AbstractPulmonary arterial hypertension (PAH) is a group of diseases with an increase of pulmonary artery pressure (PAP) and pulmonary vascular resistance. Here, the effects of safflower injection, a preparation of Chinese herbs, was investigated in a monocrotaline (MCT)-induced PAH rat model. PAP, carotid artery pressure (CAP), and the right ventricular hypertrophy index (RVHI) increased in the PAH group, while safflower injection was able to inhibit this increase to similar levels as observed in the normal group. The arteriole wall of the lungs and cardiac muscle were thickened and edema was observed in the PAH group, while these pathologies were improved in the herb-treated group in a dose-dependent manner. MCT treatment induced proliferation of pulmonary artery smooth muscle cells (PASMCs), which was inhibited by safflower injection in a dose-dependent manner. Our experimental results demonstrated that safflower injection can regulate pulmonary arterial remodeling through affecting the expression of connective tissue growth factor, transforming growth factor-β, integrin, collagen or fibronectin, which subsequently affected the thicknesses of the arteriole walls of the lungs and cardiac muscle, and thereby benefits the control of PAH. This means safflower injection improved the abnormalities in PAP, CAP and RVHI, and pulmonary arterial remodeling through regulation of remodeling factors.

Controllable signal molecule release from Au NPs-gated MSN for photocathodic detection of ultralow level AβO

2022 ◽  
Author(s):  
Xuechen Zhang ◽  
Jinling Zhang ◽  
Yao Gao ◽  
Jianyue Yan ◽  
Wenbo Song
Keyword(s):  
Controlled Release ◽  
Signal Molecule ◽  
Au Nps ◽  
Release System ◽  
Highly Sensitive ◽  
Controlled Release System

By integrating target-responsive MSN-based controlled release system with sensitization-SPR co-enhanced thinoine/MoS2 QDs/Cu NWs photocathode, a highly sensitive split-type PEC aptasensing platform for AβO detection in blood is constructed. Ultralow detection...

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