Astrocyte activity and autophagy after radiation-induced brain injury in rats

AIM: To investigate the activity of astrocytes and autophagy-related changes after radiation-induced brain injury (RBI) in rats.METHODS: A total of 36 Sprague-Dawley rats, weighing 180~200 g, were trained for 4 d in the Morris water maze. They were randomly divided into sham group, model group and 3-methyladenine (3-MA) group. The rats in model group and 3-MA group were given single whole-brain X-ray irradiation at a dose of 20 Gy after intraperitoneal anesthesia. After the irradiation was completed, the rats in model group was given 5 μL of NaCl into the lateral ventricle, and the rats in 3-MA group was injected with 3-MA at 600 nmol into the lateral ventricle. After 8 weeks of feeding, Morris water maze was used for measuring the learning and memory abilities. The brain tissues were taken and HE staining was used to observe the pathological changes of the hippocampus. The protein level of GFAP was determined by immunohistochemistry and Western blot for evaluating astrocyte activity. Dual fluorescence staining of GFAP and LC3 was performed for evaluating the changes of autophagy in the astrocytes. The protein level of cleaved caspase-3 detected by Western blot and TUNEL staining in the ipsilateral hippocampus were used to evaluate the apoptosis. The contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined by ELISA to assess the inflammatory response in the hippocampus.RESULTS: Radiation inhibited astrocyte activity, activated autophagy in astrocytes, and aggravated brain damage. 3-MA promoted the activation of astrocytes and promoted the repair of brain tissue damage.CONCLUSION: The injury of rat hippocampus after radiation is obvious, and the number of astrocytes is significantly reduced. 3-MA significantly attenuates the damage. This finding may provide a new approach for the treatment of radiation-induced brain injury.     

国医大师张学文辨治脑萎缩经验

国医大师张学文认为脑萎缩的中医病机主要是肾虚血瘀、气虚血瘀、颅脑水瘀导致脑髓失于精血濡养，脑髓不健。髓海不足和脑髓不健是本，脑络痹阻、清阳不升、浊气不降是标，本病往往虚实夹杂，纯虚者少，虚中夹实者多。宜滋肾荣脑，治当补气和血、祛瘀利水、解郁化痰、益肾活血。     

参附养心汤对老年阳虚水泛型慢性心力衰竭患者心功能及血清IL-6、TNF-α、hs-CRP水平的影响

目的 观察参附养心汤治疗老年阳虚水泛型慢性心力衰竭的临床效果。方法 将老年阳虚水泛型慢性心力衰竭患者92例随机分为观察组和对照组，每组46例。对照组采用西医常规治疗，观察组在对照组治疗方法基础上给予参附养心汤治疗。治疗4周后，对两组患者临床疗效、脑钠肽（BNP）、6 min步行距离、心功能指标[左心室舒张末期容积（LVEDV）、收缩末期容积（LVESV）、左心室射血分数（LVEF）]及细胞炎性因子[白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）、超敏C-反应蛋白（hs-CRP）]进行比较。结果 治疗4周后，观察组总有效率为89.1%，显著高于对照组71.7%，差异具有统计学意义（P<0.05）；观察组的BNP水平显著低于对照组，而6 min步行距离显著高于对照组，差异具有统计学意义（P<0.05）；观察组的LVEDV、LVESV均显著低于对照组，而LVEF高于对照组，差异具有统计学意义（P<0.05）；观察组的血清hs-CRP、IL-6及TNF-α水平均显著低于对照组，差异具有统计学意义（P<0.05）。结论 参附养心汤能显著改善老年阳虚水泛型慢性心力衰竭患者的心功能指标，降低BNP水平，减轻炎症反应，提高运动耐量，疗效显著。     

基于伏痰理论辨治精神疾病——中医脑病理论与临床实证研究（十一）

伏痰是精神疾病发病的内在因素，痰阻脑窍神机失司是其关键病机，伏痰与精神疾病的种类、发病、症状、演变等有关。本文通过精神分裂症现症期、精神分裂症伴精神发育不全、双相情感障碍伴躁狂发作、重症抑郁症、中毒性脑白质病精神障碍5个医案，阐述了精神疾病祛痰开窍醒脑安神以治标、见痰休治痰必治本、治痰饮当以温药和之的临床体会。     

Possible involvement of PKC/MAPK pathway in the regulation of GnRH by dietary arachidonic acid in the brain of male tongue sole Cynoglossus semilaevis

Our previous studies have indicated that dietary arachidonic acid (ARA) significantly affects the gonadal steroidogenesis in the marine teleost tongue sole Cynoglossus semilaevis, and this effect was more positive in male fish than in female fish (Aquaculture, 468, 378–385). As a following up study, the present study was further aimed at investigating the possible mechanisms in the brain mediating the effects of dietary ARA on gonadal steroidogenesis. A 70‐day feed trial was repeated with two‐year‐old tongue sole, using three experimental diets with graded levels of ARA, 0.34%, 2.53%, and 9.63% of total fatty acids. Each diet was fed to triplicate groups of 23 fish (15 males and 8 females). The results confirmed the positive effect of dietary ARA on testosterone production in male fish. The concentration of gonadotrophin‐releasing hormone (GnRH) in serum responded to dietary ARA in a similar pattern with the testosterone concentration, but the concentration of gonadotrophin in serum was not affected by dietary ARA. The response of gene expression of PKCβ, ARRB1, ARRB2, ERK2 and ATF3 in the brain to dietary ARA was in good agreement with those of GnRH and testosterone, indicating the possible involvement of PKC‐ARRB‐ERK‐ATF3 pathway in signalling transduction of GnRH. However, the PI3K/Akt and TLR/NF‐κB pathways may not be directly involved in the regulation of GnRH metabolism by ARA. This is the first study reporting the possible involvement of PKC/MAPK pathways in regulation of reproductive endocrine processes by long‐chain polyunsaturated fatty acid in brain of marine fish.     

Using fish models to investigate the links between microbiome and social behaviour: The next step for translational microbiome research?

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish models and their potential for advancing research fields, linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish (Danio rerio, Cyprinidae), sticklebacks (?Gasterosteidae), guppies (Poeciliidae) and cleaner–client dyads (e.g., obligate cleaner fish from the Labridae and Gobiidae families and their visiting clientele), will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades. The diversity of fish behaviour warrants more interdisciplinary research, including microbiome studies, which should have a strong ecological (field‐derived) approach, together with laboratory‐based cognitive and neurobiological experimentation. The implications of such integrated approaches may be of translational relevance, opening new avenues for future investigation using fish models.     

INTRAARTERIAL INJECTION OF IODINATED CONTRAST MEDIUM FOR CONTRAST ENHANCED COMPUTED TOMOGRAPHY OF THE EQUINE HEAD

Minimizing the volume of contrast administered for contrast‐enhanced computed tomography (CT) of the equine head is desirable for reducing costs and risks of adverse reactions, however evidence‐based studies on the effects of varying volumes on image quality are currently lacking. The objective of the current study was to determine whether low‐volume intraarterial administration of contrast medium would result in an equivalent image quality and tissue attenuation vs. high‐volume intravenous bolus administration. A prospective cross‐over experimental design was used in a sample of six horses. After anesthetic induction, the right carotid artery was exposed surgically and catheterized. Four CT scans of the cranium were performed for each horse: baseline, immediately following intraarterial contrast injection, five‐min postinjection (return to baseline) and a final scan after intravenous contrast administration. Soft tissue attenuation in predetermined regions of interest (ROI); and length, width, and height measurements of the pituitary gland were recorded at each time point. Horses were euthanized and measurements of the pituitary gland were repeated postmortem. No adverse reactions to contrast administration were observed. Intraarterial and intravenous administration of contrast medium resulted in significantly greater soft tissue enhancement of some brain ROI's and the pituitary gland vs. baseline values. Pituitary gland measurements made on postcontrast CT images did not differ from those obtained during postmortem examination. Findings indicated that low‐dose intraarterial administration of contrast material in the equine head resulted in comparable soft tissue enhancement vs. high volume intravenous administration.     

Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method

In the present study, we are reporting permeability and pharmacokinetics of nobiletin in rat plasma and brain, using a validated reverse phase high performance liquid chromatographic method. Protein precipitation method was used for the extraction of nobiletin and coumarin (IS) from rat plasma and brain tissue. The system was run in isocratic mode with mobile phase consisting of potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was proved to be accurate and precise at linearity range of 0.05–10 μg/mL with a correlation coefficient (r) of ≥ 0.994 in rat plasma and ≥ 0.995 in rat brain. The intra- and inter-day precision and accuracy values are found to be within the assay variability limits as per the FDA guidelines. Nobiletin was found stable in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and long term storage in a freezer at − 70 ± 10 °C. Maximum concentrations of nobiletin in both plasma and brain were observed at 1 h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 μg/mL, respectively. The AUC_0–t in plasma and brain were 7.49 and 20.66 μg·h/mL, respectively. The mean elimination half life (t_1/2) in plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be high at both pH 4.0 and 7.0.     

三种有机磷农药胚胎期暴露对新生鼠脑组织结构的影响

探讨了3种常用的有机磷农药胚胎期暴露对新生鼠脑组织结构的影响。在母鼠妊娠期7.5～11.5 d时,连续5 d每天分别经皮下注射2 mg/kg bw的二嗪磷(diazinon)、2 mg/kg bw的毒死蜱(chlorpyrifos)及50 mg/kg bw乙酰甲胺磷(acephate),显微镜下观察并计数大脑皮层S1区胶质细胞和神经元数量及比率,以及海马CA1、CA3区锥体细胞的数量及体积密度。结果表明,二嗪磷与毒死蜱处理分别使得大脑皮层S1区胶质细胞数减少了14.29%和21.43%;毒死蜱处理导致胶质细胞与神经元比率下降了24.19%;二嗪磷与毒死蜱处理后海马CA1区锥体细胞数量分别下降了9.30％与20.93％,毒死蜱处理后锥体细胞体积密度下降了27.05％;二嗪磷与毒死蜱处理后海马CA3区锥体细胞数量分别下降了22.22％和19.44％,锥体细胞体积密度分别下降了23.54％和18.98％;而乙酰甲胺磷对新生鼠大脑皮层与海马细胞均无明显影响。