a-modified-model-preparation-for-middle-cerebral-artery-occlusion

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug ...

cerebral-ischemic-coma-model-induced-by-modified-four-vessel-occlusion

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model ...

Foshan University

Benzoinum (Styraceae) is a traditional Chinese medicine used to treat stroke and other cardio-cerebrovascular diseases for thousands of years. Benzoinum has also proven to have diverse pharmacological activity, but the neuroprotection mechanism of apoptosis in ischaemic stroke was not determined.

Benzoinum from Styrax tonkinensis (Pierre) Craib ex Hart exerts a NVU protective effect by inhibiting cell apoptosis in cerebral ischaemia rats.

The Chinese medicines Borneolum and l-Borneolum have neuroprotective effects on acute cerebral ischaemia-reperfusion (IR) in rats. Research on their effects during recovery from cerebral IR is lacking. Cerebral ischaemia can activate astrocytes for conversion into neurons. Neurogenesis cannot be achieved without nutritional support from an improved brain microenvironment through the blood circulation.

l-Borneol and d-Borneol promote transdifferentiation of astrocytes into neurons in rats by regulating Wnt/Notch pathway to exert neuroprotective effect during recovery from cerebral ischaemia.

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol &gt; synthetic borneol &gt; natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

[Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats].

Our previous study showed l-borneol reduced cerebral infarction in the acute stage after cerebral ischemia, but there is little about the study of subacute phase. We herein investigated the cerebral protective effects of l-borneol on neurovascular units (NVU) in the subacute phase after transient middle cerebral artery occlusion (t-MCAO). The t-MCAO model was prepared by the line embolus method. Zea Longa, mNss, HE, and TTC staining were used to evaluate the effect of l-borneol. We evaluated the mechanisms of l-borneol on inflammation, p38 MAPK pathway, and apoptosis, etc. through various technologies. l-borneol 0.2, 0.1, 0.05 g·kg could significantly reduce cerebral infarction rate, alleviate the pathological injury, and inhibit inflammation reaction. l-borneol could also significantly increase brain blood supply, Nissl bodies, and the expression of GFAP. Additionally, l-borneol activated the p38 MAPK signaling pathway, inhibited cell apoptosis, and maintained BBB integrity. l-borneol had a neuroprotective effect, which was related to activating the p38 MAPK signaling pathway, inhibiting inflammatory response and apoptosis, and improving cerebral blood supply to protect BBB and stabilize and remodel NVU. The study will provide a reference for the use of l-borneol in the treatment of ischemic stroke in the subacute phase.

l-borneol promotes neurovascular unit protection in the subacute phase of transient middle cerebral artery occlusion rats: p38-MAPK pathway activation, anti-inflammatory, and anti-apoptotic effect.

Chiral drugs generally exhibit differences in activity because they bind differently to their target receptor. The Chinese medicine borneol ('Bing Pian' in Chinese) is a bicyclic monoterpenoid with a wide range of biological activities. Three kinds of Chinese medicines comprising borneol are used clinically, namely, L-Borneolum ('Ai Pian' in Chinese), Borneolum ('Tian Ran Bing Pian' in Chinese), and synthetic borneol ('He Cheng Bing Pian' in Chinese). The three kinds of borneol have different stereochemical configurations, but their clinical uses are nearly identical, and their prices vary widely. However, there is no clear rational basis for the selection of these kinds of borneol in clinical applications.

Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities.

To systematically evaluate the therapeutic effect of BaitouWeng Decoction in patients with ulcerative colitis (UC), evaluate its safety and effectiveness, and provide a reference for clinical medication.

Qian Xie

School of Medicine

Foshan University

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion

Cerebral Ischemic Coma Model Induced by Modified Four-Vessel Occlusion