Microglia:a promising therapeutic target in spinal cord injury

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

Learning to become addicted,one synapse at a time

Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli et al.,2022).

Assessment of hindlimb motor recovery affer severe thoracic spinal cord injury in rats: classification of CatWalk XT■ gait analysis parameters

Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT■gait analysis. To determine the potential bias from weight changes, corrected hindlimb(H) values(divided by the unaffected forelimb(F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT■parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwards. Of note, corrected values(H/F) of CatWalk XT■parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT■parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT■gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT■parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency.

Modalities of testing Helicobacter pylori in patients with nonmalignant bile duct diseases

AIM: This paper describes the procedure of detection ofHelicobacter pylori ( H. pylori) in bile specimens in patientssuffering from benign diseases of biliary ducts (lithiasiswith/without nonspecific cholangitis).METHODS: The group of 72 patients entering the studyconsisted of 32 male and 40 female (45 % and 55 %,respectively). Bile was obtained during ERCP in 68 patients,and during cholecystectomy in 4 patients. A fast urease test(FUT) to determine the existence of H. pylori in gastricmucosa was carried out for all the patients during theendoscopic examination. The existence of genetic materialof H. pylori was determined by detection of ure A gene bythe method of nested PCR. The results of this reaction wereshown by electrophoresis on l0 g@ L-1 agarose gel in a bandof 256 bp.RESULTS: The majority of the patients included in our studyhad biliary lithiasis without signs of cholangitis (48 patients,67 %), whereas other patients were complicated bycholangitis (17 patients, 24 %). Seven patients (9 %) hadnormal ERCP, forming thus the control group. In the groupof patients with lithiasis 26 patients (54.2 %) had positivePCR of H. pylori in bile and among the patients withassociated cholangitis positive PCR was detected in 9patients (52.9 % ). Among the seven patients with nornalERCP only one (14 %) had positive PCR of H. pylori. Ahigh percentage of H. pylori infection of gastric mucosawas observed (57 patients, 79 % ) : It was also observed thatits slightly higher positivity was in the patients with distinctbile pathology: 81% FUT positive patients in the group withcholedocholithiasis alone and 76 % in the group withcholedocholithiasis associated with cholangitis. Seventy-onepercent of the patients with regular findings had positive FUT.CONCLUSION: The prevalence of H. pylori infection both inbile and in gastric mucosa in patients with benign diseasesof biliary ducts does not show a statistically significantdifference in relation to the prevalence of the same with thepatients with normal ERCP. The existence of H. pyloriinfection possibly does not play a role in pathogenesis ofbenign biliary diseases.

The growth of Staphylococcus aureus and Escherichia coli in low-direct current electric fields

Electrical potentials up to 800 mV can be observed between different metallic dental restorations. These potentials produce fields in the mouth that may interfere with microbial communities. The present study focuses on the impact of different electric field strengths （EFS） on the growth of Staphylococcus aureus （ATCC 25923） and Escherichia coil （ATCC 25922） in vitro. Cultures of S. aureus and E. coil in fluid and gel medium were exposed to different EFS. Effects were determined by calculation of viable counts and measurement of inhibition zones. In gel medium, anodic inhibition zones for S. aureuswere larger than those for E. coliat all field strength levels. In fluid medium, the maximum decrease in the viable count of S. aureus cells was at 10 V.m-1. Field-treated S. aureus cells presented ruptured cell walls and disintegrated cytoplasm. Conclusively, S. aureus is more sensitive to increasing electric field strength than E. coll.

Interleukin 4-induced neuroprotection and regulation of microglia activation as a therapeutic approach in the MPTP model of Parkinson's disease

Parkinson＇s disease （PD） has been described as one of the most common neurodegenerative diseases affecting up to 2% of the worldwide population over 60 years of age. The hallmarks of PD are progressive loss of midbrain dopaminergic （mDA） neurons and a decrease in striatal dopamine levels, which result in typ- ical clinical motor symptoms such as akinesia, resting tremor, rigidity, and gait impairments. Although the causes for PD are only partially understood and seem to be very heterogeneous, one of the common phenomenons observed in toxin-based an- imal models of PD as well as PD patients is a microglia-driven neuroinflammatory response,

Superparamagnetic iron oxide nanoparticles: promote neuronal regenerative capacity?

Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix proteins（O’Donnell et al.,2009）.Furthermore,the discovery of a broad spectrum of growth-promoting cues has led to novel concepts for thera-peutic strategies.

Gallbladder villous adenoma in a patient with acromegaly:A case report

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecifi c gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large (4.5 cm), hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After fi ve years of follow-up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.

电碳酸氢钠协同转运蛋白1(NBCe1)在小鼠皮质星形胶质细胞中的功能性表达依赖于S255-257并受mTOR调节

电碳酸氢钠协同转运蛋白1,NBCe1(SLC4A4)是星形胶质细胞中表达的主要碳酸氢根转运蛋白。它对碳酸氢根高度敏感,并且是细胞内、细胞外和突触pH值的主要调节剂,从而调节神经元兴奋性。尽管已知NBCe1的这些基本功能,然而NBCe1介导的星形胶质细胞对细胞外pH值变化反应的分子机制尚不明确。使用原代小鼠皮质星形胶质细胞培养,本研究探索长期细胞外代谢碱中毒对NBCe1调节的影响;并通过免疫印迹,表面蛋白的生物素化,使用H+敏感染料2,7-双(羧乙基)-5-(6)-羧基荧光素记录细胞内H+,和磷酸化蛋白质组学分析阐明该调节作用潜在的分子机制。结果显示代谢性碱中毒后NBCe1活性显著下调,而NBCe1的蛋白质丰度或表面表达并不受影响。在碱中毒期间,NBCe1活性下调时细胞内H+变化的速率在野生型星形胶质细胞中降低,但在NBCe1缺陷小鼠的皮质星形胶质细胞中不变。激活mTOR信号传导能够拯救碱中毒诱导的NBCe1活性降低。此外,质谱分析揭示S255-257的组成型磷酸化,而突变分析揭示这些残基对NBCe1转运活性至关重要。本研究证明了一种通过调节NBCe1的功能表达而实现的新的mTOR调节机制。该种机制不仅适用于星形胶质细胞,也适用于上皮细胞中的NBCe1。

Controlling glutathione entry into mitochondria:potential roles for SLC25A39 in health and(treatment of)disease

Members of the mitochondrial solute carrier(SLC)family 25(SLC25)provide transport steps for substances across the mitochondrial inner membrane into the mitochondria that are needed for biochemical pathways and cellular homoeostasis.In a recent paper in Nature,Wang et al.1 could demonstrate that glutathione(GSH)transport seems to be mediated by SLC25A39,since loss of SLC25A39 reduces mitochondrial GSH import and abundance without affecting cellular GSH levels.

Joint Multi-modal Parcellation of the Human Striatum:Functions and Clinical Relevance

The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is known to consist of structurally and functionally divergent subdivisions.However,previous parcellations are based on a single neuroimaging modality,leaving the extent of the multi-modal organization of the striatum unknown.Here,we investigated the organization of the striatum across three modalities—resting-state functional connectivity,probabilistic diffusion tractography,and structural covariance—to provide a holistic convergent view of its structure and function.We found convergent clusters in the dorsal,dorsolateral,rostral,ventral,and caudal striatum.Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions,while the caudal striatum was related to action execution.Interestingly,significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ,but atrophy in the dorsolateral striatum was specifically attributable to PD.Our study revealed a cross-modal convergent organization of the striatum,representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.