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1.
Curr Med Sci ; 40(4): 699-707, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32862381

ABSTRACT

Dexmedetomidine (DEX), a potent and highly selective agonist for α2-adrenergic receptors (α2AR), exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca2+ influx. However, the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation (OGD/R) injury in vitro are unknown. We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells, as evidenced by decreased oxidative stress, autophagy, and neuronal apoptosis. Specifically, DEX pretreatment decreased the expression levels of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), and reduced the concentration of intracellular calcium pools. In addition, variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions, which were modulated through STIM1/Orai1 signaling. Moreover, DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3), hallmark markers of autophagy, and the formation of autophagosomes. In conclusion, these results suggested that DEX exerts neuroprotective effects against oxidative stress, autophagy, and neuronal apoptosis after OGD/R injury via modulation of Ca2+-STIM1/Orai1 signaling. Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.


Subject(s)
Calcium Signaling/drug effects , Dexmedetomidine/pharmacology , Neuroprotective Agents/pharmacology , ORAI1 Protein/metabolism , Reperfusion Injury/prevention & control , Stromal Interaction Molecule 1/metabolism , Animals , Apoptosis/drug effects , Autophagy/drug effects , Gene Expression Regulation/drug effects , Models, Biological , Oxidative Stress/drug effects , PC12 Cells , Rats , Reperfusion Injury/chemically induced
2.
Neural Regen Res ; 15(10): 1807-1813, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32246621

ABSTRACT

Activin receptor-like kinase 1 (ALK1) is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta (TGFß) receptor superfamily. ALK1 is specifically expressed in vascular endothelial cells, and its dynamic changes are closely related to the proliferation of endothelial cells, the recruitment of pericytes to blood vessels, and functional differentiation during embryonic vascular development. The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells. Indeed, mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation. Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms, arteriovenous malformations, and cerebral atherosclerosis. In this review, we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis, and we discuss its relationship to functional dysregulation in cerebrovascular diseases. This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis, treatment, and prevention.

3.
Oncotarget ; 8(58): 98242-98257, 2017 Nov 17.
Article in English | MEDLINE | ID: mdl-29228686

ABSTRACT

Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro, NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy.

4.
Zhonghua Yan Ke Za Zhi ; 45(9): 823-6, 2009 Sep.
Article in Chinese | MEDLINE | ID: mdl-20137289

ABSTRACT

OBJECTIVE: To design the robotic mechanism of the cornea grafting micro-surgery system and evaluate its experimental feasibility and efficacy. METHODS: It was an experimental study. Based on computer assisted cornea grafting surgery (CACGS), the prototype about cornea grafting robot, which consists of six subsystems, was developed. The system was used for looping incision and suturing for 20 rabbit corneas. Experimental data were studied including the error of target incision position, the actual cutting depth and the cutting edge span in order to evaluate the system's clinical value. All above statistical descriptions were performed using SPSS software version 11.5. RESULTS: 20 corneas were looping incised and sutured by the robot-assisted cornea grafting micro-surgery system successfully. The error of target incision position was (0.356 + or - 0.040) mm. With CACGS, the cutting edge span (A) was (0.855 + or - 0.040) and the actual cutting depth error was less than 10 microm. Corneal structure and thickness was showed no change and cutting edge of cornea was displayed regularity in pathological examination. To suturing system, suturing span was (2.15 + or - 0.09) mm and the error of span (0.15 + or - 0.02) mm. CONCLUSIONS: The cornea grafting micro-surgery system developed is used for cornea grafting of some animals successfully. The experiment results demonstrate the stability and efficiency of the robot.


Subject(s)
Corneal Transplantation/instrumentation , Robotics , Animals , Microsurgery , Models, Animal , Rabbits , Suture Techniques
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