Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine‐related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5‐day withdrawal period. In addition, c‐Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c‐Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Synapse 67:553–567, 2013. © 2013 Wiley Periodicals, Inc.     

Impairment of change in diameter of the hepatic portion of the inferior vena cava: a sonographic sign of liver fibrosis or cirrhosis.

OBJECTIVE: We propose a new sonographic technique for detecting parenchymal stiffness of the liver. This technique measures the physiologic change in the diameter of the hepatic inferior vena cava (IVC). The hepatic portion of the IVC is extensively attached to the hepatic parenchyma so that changes in diameter of the venous lumen could not occur without changes in the shape of the surrounding parenchyma. Therefore, increased parenchymal stiffness due to cirrhosis or fibrosis may result in an impaired change in venous diameter. METHODS: Thirty patients with histologically proven cirrhosis and 30 patients with normal livers were examined. A commercial ultrasound system was used in conjunction with a convex probe at a center frequency of 4.0 MHz. The major axis of the IVC was measured during normal breathing. The patients were then requested to take a deep breath to produce negative intrathoracic pressure, and the same measurement as that during normal breathing was repeated immediately. RESULTS: In the normal liver group, the maximal diameter of the vena cava was 2.35 +/- 0.34 cm (mean +/- SD), and this was reduced by 1.30 +/- 0.67 cm (range, 0.4-2.85 cm) during deep inspiration. In the cirrhotic patient group, the maximal diameter was 1.74 +/- 0.35 cm, and this was reduced by 0.03 +/- 0.09 cm (range, 0.0-0.4 cm) (P < .0001). CONCLUSIONS: The physiologic change in the diameter of the hepatic portion of the IVC enhanced by deep respiration may reflect the stiffness of hepatic parenchyma.     

Neurochemical correlates of caudate atrophy in Huntington's disease

The precise pathogenic mechanisms of Huntington's disease (HD) are unknown but can be tested in vivo using proton magnetic resonance spectroscopy (¹H MRS) to measure neurochemical changes. The objective of this study was to evaluate neurochemical differences in HD gene mutation carriers (HGMCs) versus controls and to investigate relationships among function, brain structure, and neurochemistry in HD. Because previous ¹H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two ¹H MRS data analysis approaches. HGMCs with premanifest to early HD and controls underwent evaluation of motor function, magnetic resonance imaging, and localized ¹H MRS in the caudate and the frontal lobe. Analytical approaches that were tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). We identified a suite of neurochemicals that were reduced in concentration proportionally to loss of caudate volume in HGMCs. Caudate concentrations of N‐acetylaspartate (NAA), creatine, choline, and caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and glutamate were correlated with caudate volume in HGMCs. The relative, but not the absolute, quantitation approach revealed disease‐related differences; the Glx signal was decreased relative to other neurochemicals in the caudate of HGMCs versus controls. This is the first study to demonstrate a correlation among structure, function, and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable the magnification of subtle differences between groups. Observation of decreased Glx suggests that glutamate signaling may be disrupted relatively early in HD, which has important implications for therapeutic approaches. © 2014 International Parkinson and Movement Disorder Society     

A cholangiocellular carcinoma radically resected by central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct

A case of cholangiocellular carcinoma, involving the hepatic hilus, radically resected by central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct is presented. Preoperative surgical planning was carried out on the basis of an evaluation of the findings of ultrasonography, computed tomography, angiography, percutaneous transhepatic portography, and tube cholangiography. The operation lasted for 16 h and 15 min, with 5700 g blood loss. Postoperative recovery was very good and the patient has now been well for 26 months after surgery. Although the surgical technique of central hepatic bisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile duct is very difficult, this procedure should be indicated for selected cases of cholangiocellular carcinoma involving the hepatic hilus.     

Changing the mind? Not really—activity and connectivity in the caudate correlates with changes of choice

Changes in preference are inherently subjective and internal psychological events. We have identified brain events that presage ultimate (rather than intervening) choices, and signal the finality of a choice. At the first exposure to a pair of faces, caudate activity reflected the face of final choice, even if an initial choice was different. Furthermore, the orbitofrontal cortex and hippocampus exhibited correlations only when the subject had made a choice that would not change.     

Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine

Methamphetamine (m-AMPH) treatment produces long-lasting damage to striatal and cortical monoaminergic terminals and may also injure nonmonoaminergic cortical neurons. Evidence suggests that both dopamine (DA) and glutamate (GLU) play crucial roles in producing this damage. We used quantitative autoradiography to examine [³H]mazindol ([³H]MAZ) binding to striatal DA transporters and [³H]GLU binding to N-methyl-D-aspartate (NMDA) receptors in the striatum and cortex 1 week and 1 month after a neurotoxic regimen of m-AMPH. Rats received m-AMPH (4 mg/kg) or saline (SAL) (1 ml/kg) in four s.c. injections separated by 2 h intervals. One week after m-AMPH, the ventral and lateral sectors of the striatum showed the greatest decreases in both [³H]MAZ and [³H]GLU binding, while the nucleus accumbens (NA) showed no significant decreases. One month after m-AMPH, striatal [³H]MAZ binding was still significantly decreased, while NMDA receptor binding had recovered. Surprisingly, the parietal cortex showed a m-AMPH-induced increase in NMDA receptor binding in layers II/III and IV 1 week after m-AMPH and only in layers II/III 1 month after m-AMPH. The prefrontal cortex showed no m-AMPH-induced changes in NMDA receptor binding at either time point. This is the first demonstration that a regimen of m-AMPH that results in long-lasting damage to DA terminals can alter forebrain NMDA receptor binding. Thus, repeated m-AMPH treatments may produce changes in glutamatergic transmission in selected striatal and cortical regions. © 1996 Wiley-Liss, Inc.     

蛋白-蛋白相互作用调节多巴胺受体D3的功能(英文)

Gαi/o蛋白偶联的多巴胺受体D3在包括付隔核的边缘系统中丰富表达。其不仅能调节边缘系统功能,而且在神经精神疾病和神经退行性病变过程中起重要作用。D3受体的胞内结构,尤其是第三个细胞内环和C末端,可以和多个靠近细胞内膜的蛋白相互结合,以此来调控受体的膜表面表达及其功效。最近的研究发现,D3受体和蛋白激酶能够以此模型相互结合。突触富集的钙/钙调蛋白依赖的蛋白激酶II(CaMKII)直接与D3受体第三个细胞内环的N末端结合。这种结合是钙离子依赖的,并被CaMKII激酶的自我磷酸化所加强。在大鼠的付隔核神经元中,钙离子水平的升高能诱导CaMKII与D3结合,并磷酸化D3受体上特定的丝氨酸位点。CaMKII介导的受体磷酸化能抑制受体的功能,进而调节动物对可卡因兴奋剂的行为学反应。这些结果揭示了G蛋白偶联受体与CaMKII作用的一种新模式。蛋白间动态的结合使得D3受体的膜表达丰度、衰减周期和功能受到多种信号和酶蛋白的调节。     

Encoding and retrieval of landmark‐related spatial cues during navigation: An fMRI study

To successfully navigate, humans can use different cues from their surroundings. Learning locations in an environment can be supported by parallel subsystems in the hippocampus and the striatum. We used fMRI to look at differences in the use of object‐related spatial cues while 47 participants actively navigated in an open‐field virtual environment. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the removed target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. Participants were informed in blocks about which type of retrieval trial was most likely to occur, thereby modulating expectations of having to rely on a single landmark or on a configuration of landmarks. How the spatial learning systems in the hippocampus and caudate nucleus were involved in these landmark‐based encoding and retrieval processes were investigated. Landmark configurations can create a geometry similar to boundaries in an environment. It was found that the hippocampus was involved in encoding when relying on configurations of landmarks, whereas the caudate nucleus was involved in encoding when relying on single landmarks. This might suggest that the observed hippocampal activation for configurations of objects is linked to a spatial representation observed with environmental boundaries. Retrieval based on configurations of landmarks activated regions associated with the spatial updation of object locations for reorientation. When only a single landmark was available during retrieval, regions associated with updating the location of oneself were activated. There was also evidence that good between‐participant performance was predicted by right hippocampal activation. This study therefore sheds light on how the brain deals with changing demands on spatial processing related purely to landmarks. © 2014 Wiley Periodicals, Inc.     

腹腔镜肝尾状叶切除的单中心经验

目的探讨腹腔镜肝尾状叶切除的手术技巧,回顾性分析18例腹腔镜单独肝尾状叶切除术的临床疗效。 方法2013年1月至2018年3月,18例肝尾状叶肿瘤、血管瘤或局灶性结节性增生的患者采取腹腔镜肝尾状叶切除术,对其临床资料进行分析。 结果18例腹腔镜肝尾状叶切除术均成功,手术时间75～420 min ,平均126.3 min;术中出血量50～350 ml,平均87.7 ml;术后住院时间6～15 d,平均10.2 d;术后ALT、AST、TBIL在术后1 d上升,但是术后3 d及术后5 d呈下降的趋势。术后无出血、肝衰竭、感染、死亡等严重并发症。 结论腹腔镜肝尾状叶切除是安全、可行的。     

Hilar cholangiocarcinoma—surgical anatomy and curative resection

We have studied the surgical anatomy of the intrahepatic bile duct, hepatic hilus, and caudate lobe based on intraoperative findings and selective cholangiography of surgical patients and resected specimens, and have established the cholangiographic anatomy of the intrahepatic subsegmental bile duct. Thorough knowledge of the three-dimensional anatomy of the subsegmental bile duct, hepatic hilus, and caudate lobe is indispensable for curative surgery of hilar cholangiocarcinoma. We designed and actually performed 15 kinds of hepatic segmentectomies with caudate lobectomy and extrahepatic bile buct resection in 100 consecutive patients, with curative resection being possible in 82 patients. Postoperative survival after curative resection of hilar cholangiocarcinoma was better than expected, and the 5-year survival rates for all 82 patients with curative resection and for 55 patients with curative surgery without portal vein resection were 31% and 43%, respectively. Hepatic segmentectomy with caudate lobectomy and extrahepatic bile duct resection should be designed not only in accordance with the preoperative diagnosis of tumor extension into the intrahepatic bile ducts but also so that curative surgery for advanced hilar cholangiocarcinoma can be performed.