The efficacy and safety of salvianolic acids on acute cerebral infarction treatment: A protocol for systematic review and meta analysis.

BACKGROUND: Salvianolic acids (SA) has been widely used for the treatment of acute cerebral infarction (ACI) combined with basic western medicine therapy in China. This study was aimed to evaluate the efficacy and safety of SA on ACI treatment and its influence on neurological functions, activity of daily living, and cognitive functions. METHODS: We retrieved related articles from PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Medline, Ovid, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database without date and language restrictions. Finally, 58 randomized controlled trials were included from 239 retrieved records. Two researchers extracted the basic information and data from included articles and assessed the quality and analysis of data by using Review Manager 5.3. RESULTS: The administration of SA significantly increased the total clinical effective rate of ACI treatment (P < .001) and improved the National Institute of Health Stroke Scale scores, modified Rankin Scale scores, and Barthel Index scores after treatment and 3 months after ACI (P < .05). The activities of daily living scores in the SA group were significantly increased after treatment (P < .001), whereas they were remarkably decreased 3 months after ACI (P < .001) compared with that in the control group. Besides, SA profoundly promoted the recovery of Montreal Cognitive Assessment scores (P < .001). However, the use of SA increased the risk of adverse events occurrence (P = .007). CONCLUSION: SA combined with basic western medicine treatment could promote neurological functions, daily living activities, and cognitive functions recovery of ACI patients. Although SA increased the risk of adverse events occurrence, these adverse events were easily controlled or disappeared spontaneously.

Cyclic adenosine monophosphate in acute ischemic stroke: some to update, more to explore.

The development of effective treatment for ischemic stroke, which is a common cause of morbidity and mortality worldwide, remains an unmet goal because the current first-line treatment management interventional therapy has a strict time window and serious complications. In recent years, a growing body of evidence has shown that the elevation of intracellular and extracellular cyclic adenosine monophosphate (cAMP) alleviates brain damage after ischemic stroke by attenuating neuroinflammation in the central nervous system and peripheral immune system. In the central nervous system, upregulated intracellular cAMP signaling can alleviate immune-mediated damage by restoring neuronal morphology and function, inhibiting microglia migration and activation, stabilizing the membrane potential of astrocytes and improving the cellular functions of endothelial cells and oligodendrocytes. Enhancement of the extracellular cAMP signaling pathway can improve neurological function by activating the cAMP-adenosine pathway to reduce immune-mediated damage. In the peripheral immune system, cAMP can act on various immune cells to suppress peripheral immune function, which can alleviate the inflammatory response in the central nervous system and improve the prognosis of acute cerebral ischemic injury. Therefore, cAMP may play key roles in reducing post-stroke neuroinflammatory damage. The protective roles of the cAMP indicate that the cAMP enhancing drugs such as cAMP supplements, phosphodiesterase inhibitors, adenylate cyclase agonists, which are currently used in the treatment of heart and lung diseases. They are potentially able to be applied as a new therapeutic strategy in ischemic stroke. This review focuses on the immune-regulating roles and the clinical implication of cAMP in acute ischemic stroke.

Astrocytic gap junction inhibition by carbenoxolone enhances the protective effects of ischemic preconditioning following cerebral ischemia.

BACKGROUND: Stroke is the second leading cause of death worldwide and the most common cause of adult-acquired disability in many nations. Thus, attenuating the damage after ischemic injury and improving patient prognosis are of great importance. We have indicated that ischemic preconditioning (IP) can effectively reduce the damage of ischemia reperfusion and that inhibition of gap junctions may further reduce this damage. Although we confirmed that the function of gap junctions is closely associated with glutamate, we did not investigate the mechanism. In the present study, we aimed to clarify whether the blockade of cellular communication at gap junctions leads to significant reductions in the levels of glutamate released by astrocytes following cerebral ischemia. METHODS: To explore this hypothesis, we utilized the specific blocking agent carbenoxolone (CBX) to inhibit the opening and internalization of connexin 43 channels in an in vitro model of oxygen-glucose deprivation/re-oxygenation (OGD/R), following IP. RESULTS: OGD/R resulted in extensive astrocytic glutamate release following upregulation of hemichannel activity, thus increasing reactive oxygen species (ROS) generation and subsequent cell death. However, we observed significant increases in neuronal survival in neuron-astrocyte co-cultures that were subjected to IP prior to OGD/R. Moreover, the addition of CBX enhanced the protective effects of IP during the re-oxygenation period following OGD, by means of blocking the release of glutamate, increasing the level of the excitatory amino acid transporter 1, and downregulating glutamine expression. CONCLUSIONS: Our results suggest that combined use of IP and CBX represents a novel therapeutic strategy to attenuate damage from cerebral ischemia with minimal adverse side effects.

Research and Clinical Application of Three-Dimensional Location of Amygdaloid Body.

Accurately representing the spatial location of the amygdaloid body can lay an anatomical basis for the neurosurgery operation for amputation of the amygdaloid body through lateral fissure approach. As we know, there are a number of nerve nucleuses and essential structures locating around amygdaloid body in our brain, especially optic tract. However, only few research had been done to protect these tissues or nerve nucleuses. Thus, we reconstructed the three-dimensional images of the amygdaloid body of the human brain and established a coordinate system. The morphological parameters of the amygdaloid body and the three-dimensional coordinate data were measured. The spherical coordinates (R, θ, ϕ) were constructed by calculating the azimuth angle, elevation angle, and the distance from the coordinates origin to each amygdaloid body centroid. Sixty people brain MRI images without any visible organic disease were used in our research to investigate the average level of related parameters. The authors selected a proper coordinate origin and measured the value of anteroposterior diameter, right-and-left diameter, vertical diameter of the amygdaloid body, and the distance from the optic tract to amygdaloid body. The authors also measured the three-dimensional coordinate data of each centroid of the amygdaloid body in order to provide anatomical suggestion for surgery. The authors confirmed the nearest point from the foremost edge of the brain ventricle temporal horn to the lateral fissure, then viewed it as the coordinate origin. By means of coordinate translation, the authors got various morphological parameters and the coordinate values of each centroid of the amygdaloid body. Spherical coordinates were calculated from the three-dimensional coordinate values. The distances between the different layers of the amygdaloid body and the optic tract were also measured. The reconstruction of the three-dimensional coordinates of amygdaloid body is part of the digital engineering of the human body. The measurement of the parameters provides an important theoretical basis for the clinical amygdaloid body destruction surgery. Finally, the authors get conclusions as follows. There are no significant differences in the measured values of r1, r2, and r3 between the upper and lower diameters, the left and right diameters, the anteroposterior diameter of the amygdaloid body. The measured values of men and women are not statistically significant (P > 0.05). Spherical coordinates (R, θ, ϕ) calculated from the three-dimensional coordinate values and values from different sexes of the amygdaloid body are not statistically significant, either (P > 0.05). The distance between the different levels of the amygdaloid body and the optic tract (h1, h2, h3, h4, h5, h6, and h7) are not statistically significant (P > 0.05).