Hemodynamic changes between different anatomically designed stents after carotid stenting: a prospective multicenter study

Journal of Neurology - The aim of this study was to investigate differences in the dynamic changes and risk factors of hemodynamic depression (HD) between straight and tapered carotid stenting (SCS...     

Effects of immunotherapies and prognostic predictors in neuromyelitis optica spectrum disorder: a prospective cohort study

Journal of Neurology - Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune demyelinating disease of the CNS, often leads to severe visual and/or motor disability. This study...     

Insights into major facilitator superfamily domain-containing protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?

Major facilitator superfamily domain-containing protein-2a (Mfsd2a) which was considered as an orphan transporter has recently gained attention for its regulatory role in the maintenance of proper functioning of the blood–brain barrier. Besides the major role of Mfsd2a in maintaining the barrier function, increasing evidence has emerged with regard to the contributions of Mfsd2a to various biological processes such as transport, cell fusion, cell cycle, inflammation and regeneration, managing tumor growth, functioning of other organs with barrier functions or responses to injury. The purpose of this article is to review the different roles of Mfsd2a and its involvement in the physiological and pathophysiological processes primarily in the central nervous system and throughout the mammalian body under the lights of the current literature.     

Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics

Intranasal recombinant osteopontin (OPN) has been shown to be neuroprotective in different models of acquired brain injury but has never been tested after traumatic brain injury (TBI). We used a model of moderate-to-severe controlled cortical impact in male adult Sprague Dawley rats and tested our hypothesis that OPN treatment would improve neurological outcomes, lesion and brain tissue characteristics, neuroinflammation, and vascular characteristics at 1 day post-injury. Intranasal OPN administered 1 hr after the TBI did not improve neurological score, lesion volumes, blood–brain barrier, or vascular characteristics. When assessing neuroinflammation, we did not observe any effect of OPN on the astrocyte reactivity but discovered an increased number of activated microglia within the ipsilateral hemisphere. Moreover, we found a correlation between edema and heme oxygenase-1 (HO-1) expression which was decreased in OPN-treated animals, suggesting an effect of OPN on the HO-1 response to injury. Thus, OPN may increase or accelerate the microglial response after TBI, and early response of HO-1 in modulating edema formation may limit the secondary consequences of TBI at later time points. Additional experiments and at longer time points are needed to determine if intranasal OPN could potentially be used as a treatment after TBI where it might be beneficial by activating protective signaling pathways.     

Brain-derived neurotrophic factor and post-stroke depression

Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also recognized with more evidence surfacing. In patients with PSD, their serum BNDF level is lower than in those without depression. Furthermore, antidepressants could enhance BDNF expression in the brain, resulting in an alleviation of depression symptoms. Such therapeutic effect can be abolished in animals with the BDNF gene deleted. In PSD patients, the presence of stroke may contribute to the development of depression, including affecting the expression of BDNF. However, the mechanisms of BDNF in the development of PSD remain largely unknown. Lower BDNF levels may have existed in some patients before stroke onset, making them vulnerable to develop depressive symptoms. Meanwhile, the hypoxic environment induced by stroke could possibly downregulate BDNF expression in the brain. Current antidepressant treatments are not specific for PSD and there is a lack of treatments to address the linkage between stroke and PSD. This review summarizes the current knowledge of BDNF in PSD. By regulating BDNF expression, a synergistic effect may be achieved when such treatments are applied together with existing antidepressants.     

Improved trafficking and expression of luminopsins for more efficient optical and pharmacological control of neuronal activity

Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provide control of neuronal activity, allowing for less cumbersome and less invasive optogenetic manipulation. It was previously shown that both an external light source and the luciferase substrate, coelenterazine (CTZ), could modulate activity of LMO-expressing neurons, although the magnitudes of the photoresponses remained subpar. In this study, we created an enhanced iteration of the excitatory luminopsin LMO3, termed eLMO3, that has improved membrane targeting due to the insertion of a Golgi trafficking signal sequence. In cortical neurons in culture, the expression of eLMO3 resulted in significant reductions in the formation of intracellular aggregates, as well as in a significant increase in total photocurrents. Furthermore, we corroborated the findings with injections of adeno-associated viral vectors into the deep layers of the somatosensory cortex (the barrel cortex) of male mice. We observed greatly reduced numbers of intracellular puncta in eLMO3-expressing cortical neurons compared to those expressing the original LMO3. Finally, we quantified CTZ-driven behavior, namely whisker-touching behavior, in male mice with LMO3 expression in the barrel cortex. After CTZ administration, mice with eLMO3 displayed significantly longer whisker responses than mice with LMO3. In summary, we have engineered the superior LMO by resolving membrane trafficking defects, and we demonstrated improved membrane targeting, greater photocurrents, and greater functional responses to stimulate with CTZ.     

Depletion of microglia in developing cortical circuits reveals its critical role in glutamatergic synapse development,functional connectivity,and critical period plasticity

Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long-lasting circuit abnormality. We administered PLX3397, a colony-stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19-32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single-unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity.     

强化血糖监测在冠脉旁路移植术后患者血糖管理中的应用

目的探讨强化血糖监测护理方案对冠脉旁路移植术(CABG)术后转入普通病房的患者血糖变异性的影响。方法采用便利抽样法,选取北京安贞医院2018年6—12月入院行CABG于72 h内转出ICU的冠心病合并高血糖患者106例,按照随机数字表法分为对照组(54例)和研究组(52例)。对照组给予常规护理,研究组在对照组的基础上采用强化血糖监测在内的综合护理策略。比较两组CABG术后患者转至普通病房3 d内每日平均血糖水平(MGL)、血糖标准差(SD)、日内平均血糖波动幅度(MAGE)、血糖变异系数(CV)。结果患者从ICU转入普通病房后的MGL存在时间效应、组间效应以及时间和组间的交互效应;SD存在组间效应;MAGE存在时间和组间效应;CV存在组间效应以及时间和组间的交互效应。结论在患者转出ICU到普通病房术后1~3 d内,与常规护理组相比较,继续给予强化血糖监测与护理能够减少血糖变异程度。