Kongsheng Zhenzhong pill's effect on the learning and memory ability and its neuroprotective effects in vascular dementia rats

Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.

Stimulating mitochondria to protect the brain following traumatic brain injury

Traumatic brain injury （TBI） is an acquired injury to the brain that occurs with sudden trauma that can range from mild （concussive） to severe. TBI is considered a leading cause of death in children and young adults, with the Centers for Disease Control and Prevention estimating that approximately 1.7 million cases of TBI occur in the United States annually （Faul et al., 2010）. Further, since the begin- ning of the global war on terrorism, the Department of Defense has reported over 344,000 U.S. Service Members have been diagnosed with traumatic brain injury from penetrating injuries to mild forms of TBI. TBI, caused by a sudden impact, penetration, or rapid move- ment of the brain, interrupts the normal functioning of the brain. While the intracranial location and severity of injury contribute to the extent of functional deficits.

Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone （8 mg/kg） at 1 （intraperitonally）, 6, 24, and 48 hours （subcutaneously） post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

A brief report on MRI investigation of experimental traumatic brain injury

Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the 2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity.

MRI-Based Patient-Specific Left Ventricular Model to Determine the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions

Introduction Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles of human heart and account for a significant portion of the ventricular mass.However,the role of trabeculae carneae in left ventricular(LV)function is not well understood.Previous reports suggested that trabeculae help squeeze blood from the apical region during systole[1].Our recent study suggests that trabeculae carneae hypertrophy and fibrosis contribute to increased LV stiffness in patients with diastolic heart failure,and severing free-running trabeculae carneae may improve diastolic compliance of the LV[2].Objective To understand the role of trabeculae carneae in the left ventricular diastolic and systolic functions using anatomically detailed patient-specific finite element models of the human LV.Methods(1)Image acquisition An explanted human heart was collected from a 63 year old female donor with a history of stroke and congestive heart failure within 24 hours postmortem from South Texas Blood and Tissue Center(San Antonio,TX).The heart was de-identified in accordance with Institutional Review Board(IRB)requirements and informed consent for research was obtained from the donor’s family.Three-dimensional MRI scanning was conducted on a 3T(128 MHz)MRI system(TIM Trio,Siemens Medical Solutions),comprised of a superconducting magnet with a 60 cm diameter accessible bore,when the heart was submerged in a saline filled plastic container.(2)Finite element analysis Three distinct LV models were derived from the MR images.The first model was the intact trabeculated model(TM)which contained all trabeculae carneae and papillary muscles.This high-resolution anatomically detailed 3D model of the LV was segmented from 2D MR images in DICOM format using Mimics(Materialise NV,Leuven,Belgium).The second model was the papillary model(PM),in which the papillary muscles remain intact but most of the trabeculae carneae were excluded in the smoothing process.The third model was the smooth model(SM)in which the trabeculae carneae and papillary muscles were excluded during image segmentation.Finite element(FE)models of the TM,PM and SM were created by meshing 3D reconstructions of the acquired MR images using tetrahedral elements(ICEM,Ansys Inc.,Canonsburg,PA).The mesh size was selected after a pilot study on mesh sensitivity.The passive cardiac muscle was characterized as a hyperelastic,incompressible,transversely isotropic material with a Fung exponential strain energy function.The material constants were determined by matching the end-diastolic pressure-volume relationship with the empirical Klotz relation[3].A rule-based myocardial fiber algorithm was adopted to generate the myofiber directions [4].The active contraction(i.e.,systolic contraction)was modeled by the time varying'Elastance'active contraction model.The contractile parameter Tmax was determined and calibrated so that the FE predicted ejection fraction(EF)of TM matched the EF of a normal human heart at the specified end-systolic pressure[3].The analysis of the TM,PM,and SM models were implemented using the open-source finite element package FEBio(www.febio.org).In all models,the rigid body motion was suppressed by constraining the base from moving in all directions.The end-diastolic and end-systolic pressure-volume relationships(EDPVR and ESPVR)were obtained and characterized by an exponential function and the slope,respectively.Results Our simulation results showed that independent of the material model,the EDPVR curve shifts to the right in PM and SM compared to TM.However,the ESPVR curve may shift to the right or left in PM compared to TM,while shifting tothe right in SM for all material models.EDPVR was steeper in TM compared to PM and SM;however,ESPVR was found to be steeper in PM than in TM and SM.The predicted parameters of EDPVR and ESPVR showed lower average exponential term in PM and SM compared to TM,indicating a significant improvement in the compliance and global diastolic function of less trabeculated LV models(P<0.01).Similarly,the higher average elastance EEs and lower volume intersect in PM compared to TM,suggests that mild cutting of trabeculae carneae slightly improves the global systolic function of the LV(P=0.89).However,cutting all trabeculae carneae and papillary muscles in SM had a significant adverse effect on the global systolic function(P<0.01).Discussion and conclusions Most patient-specific LV studies in the literature have used smoothed ventricular geometries.We used high resolution MRI to capture the endocardial details of the LV.Though reproducing very fine trabeculae carneae was restricted by the MRI resolution,our results demonstrated the importance of considering endocardial structures,i.e.papillary muscles and trabeculae carneae,in the assessment of LV global function in patient-specific computational LV models.The present work is consistent with the observation that diastolic performance improved after severing trabeculae carneae due to a reduction in LV stiffness[2].Furthermore,our results also suggest that severing trabeculae carneae(without affecting papillary muscle)may improve LV systolic function.Our model results are consistent with experimental measurements using ex vivo rabbit heart perfusion [5].This improvement would be greater in hypertrophic hearts because trabeculae carneae are also hypertrophic and more fibrotic.Left ventricular hypertrophy is often associated with heart failure with preserved ejection fraction(HFpEF).There is no effective treatment for HFpEF,which is characterized by impaired diastolic relaxation due to increased LV stiffness.Our results indicate that trabecular cutting could be an effective treatment for HFpEF.

Brain Activity in Sleep Compared to Wakefulness: A Meta-Analysis

Objective: Neuroimaging studies using a variety of techniques have been conducted in sleep to explore the changes in brain activity during the different sleep stages. The current study employed a quantitative meta-analytic technique in an attempt to integrate the findings from such studies. Methods: Using an updated version of the Activation Likelihood Estimation (ALE) method, individual meta-analyses were carried out on: 1) studies contrasting REM sleep and wakefulness, and 2) studies contrasting NREM sleep and wakefulness. Results: Based on the results of the current meta-analyses, a number of cortical and subcortical brain regions appear to be involved in sleep and sleep processes, with both decreases and increases noted across NREM and REM sleep. Specifically, areas of decreased activity comprised thalamic structures (pulvinar, dorsomedial thalamus) and frontal regions (inferior, superior, and middle frontal gyrus). Furthermore, increased and decreased activity was noted in the anterior cingulate during sleep. Conclusions: Despite limited overlap across these sleep stages among regions identified, consistent decreases were revealed in NREM sleep (thalamus) and REM sleep (frontal cortex) when compared to wakefulness. Such findings suggest that these regions may ultimately play a key role in the loss of consciousness characteristic of sleep. Further research is needed to determine if and how such activity may be related to dreaming.