Hypoxic-hemodynamic pathogenesis of brain lesions in the newborn

For more than a century two opposing views on the pathogenetic mechanisms and the timing of the origin of cerebral palsy (CP) have prevailed: the idea first formulated by Little attributing CP to “difficult deliveries” has been opposed by the view by Freud recognizing fetal influences, and the issue seems to be unsettled. The present review seeks to bridge the gap by recognizing that late prenatal or perinatal hypoxic-hemodynamic insult is a dominating final common path in the pathogenesis of static encephalopathies during development, in particular in premature infants. In turn, however, such lesions are determined by early genetic and environmental influences. The pathogenesis of static encephalopathy should therefore be seen as a chain of events, with its origin before gestation.     

早产儿脑室周围-脑室内出血预防的临床证据

目的 寻找与早产儿脑室周围-脑室内出血(PVH-IVH)预防相关的临床证据,并探讨其临床应用价值.方法 检索MEDLINE、EMBASE、Oxford围产新生儿组资料库和Cochrane图书馆关于PVH-IVH危险因素和预防相关的系统评价和随机(半随机)对照研究(randomised or quasi-randomised controlled trials,RCT),并进行分析.结果 产前母亲使用皮质激素、出生时延迟结扎脐带可显著降低早产儿PVH-IVH发生率,出生后预防性使用消炎痛可降低早产儿严重IVH的发生率,但对神经系统远期预后没有影响.结论 推荐产前母亲单次使用皮质激素预防早产儿PVH-IVH的发生,消炎痛和产前多次使用皮质激素尚待更多的前瞻性RCT来证实其安全性和有效性.     

Effects of lesions in the amygdala and periventricular hypothalamus on striatal somatostatin-like immunoreactivity

Somatostatin has been found in substantial amounts in the basal ganglia by radioimmunoassay and has been demonstrated in both neurons and nerve terminals. Since the levels of somatostatin have been shown to vary in Huntington's and Alzheimer's disease it was of interest to see whether such changes could be produced experimentally. Lesions of the periventricular nucleus of the hypothalamus and knife cuts adjacent to this nucleus had no effect on striatal somatostatin-like immunoreactivity (SLI). Similarly lesions of mediodorsal frontal cortex, and those isolating pyriform cortex or the olfactory bulb had no effect on striatal SLI. Removal of tge amygdala resulted in significant increases in SLI in the ipsilateral striatum and nucleus accumbens, suggesting loss of an inhibitory interaction. Stria terminalis lesions failed to reproduce this effect suggesting that it is mediated via amygdalo-striatal projections traveling in the dorsal longitudinal bundle. Other findings support a somatostatin projection to the amygdala from the bed nucleus of the stria terminalis and one from the amygdala to the ventromedial hypothalamus.     

Luteinizing Hormone-Releasing Hormone and Gamma-Aminobutyric Acid Neurons in the Medial Preoptic Area are Synaptic Targets of Dopamine Axons Originating in Anterior Periventricular Areas

The aim of this study was to characterize further the transmitter content and the location of the parent cells of tyrosine hydroxylase-immunoreactive boutons terminating on luteinizing hormone-releasing hormone- and glutamic acid decarboxylase-immunoreactive neurons in the rat medial preoptic area. Electron microscopic immunostaining for luteinizing hormone-releasing hormone, tyrosine hydroxylase or glutamic acid decarboxylase was performed on desipramine-pretreated (to protect norepinephrine and epinephrine axons) rats which received a stereotaxic injection of 6-hydroxydopamine into the medial preoptic area anteroventral periventricular nucleus 48 h prior to sacrifice. This treatment induced acute degeneration of dopamine axon terminals characterized by the development of autophagous cytolysosomes, an early morphological sign of catecholamine axon degeneration. To further define the cells of origin of these dopamine boutons, the anterograde marker Phaseolus vulgaris leucoagglutinin was iontophoretically applied to the zona incerta. Six days later, rats received a 6-hydroxydopamine injection into the zona incerta or the lateral ventricle, and 48 h later, double immunostaining was performed for Phaseolus vulgaris leucoagglutinin and tyrosine hydroxylase, luteinizing hormone-releasing hormone, or glutamic acid decarboxylase on preoptic area vibratome sections. Following the 6-hydroxydopamine injection into the anteroventral periventricular nucleus, autophagous cytolysosome-containing degenerated axons were found in synaptic contact with both luteinizing hormone-releasing hormone and GABA neurons in the medial preoptic area, confirming that these are dopaminergic connections. Following the double injection treatment, 6-hydroxydop-amine-induced degenerated, Phaseolus vulgaris leucoagglutinin-labeled dopamine axons originating in the zona incerta were not found to contact luteinizing hormone-releasing hormone-containing or GABA cells. Instead, many degenerated, Phaseolus vulgaris leucoagglutinin-immunopositive boutons were observed in the dorsomedial and paraventricular nuclei of the hypothalamus. These observations indicate that tyrosine hydroxylase-immunoreactive fibers terminating on the medial preoptic area luteinizing hormone-releasing hormone and GABA cells are dopaminergic and most probably originate from dopamine neurons located in anterior periventricular areas of the hypothalamus.     

Some cellular characteristics of somatostatin neurons and terminals in the periventricular nucleus of the rat hypothalamus and median eminence. Electron microscopic immunohistochemistry

Somatostatin neuronal perikarya and their processes, presumably dendrites, in the periventricular nucleus of the rat hypothalamus and terminals in the median eminence were observed by electron microscopic immunohistochemistry. Neuronal perikarya and processes contained immunoreactive dense granules (100-120 nm in diameter) and other cellular components such as polysomes, rER membranes occasionally showed high electron density. Few axo-somatic terminals were found on the somatostatin neurons, but we could detect a number of preterminal axons on immunoreactive processes, presumably dendrites. Therefore, we considered that somatostatin neurons receive mainly neuronal input through axo-dendritic synapses rather than through axo-somatic ones. In the somatostatin terminals in the external layer of the median eminence immunoreactivity was completely restricted on the granules.     

Localization of salmon calcitonin binding sites in rat brain by autoradiography

The presence of corticotropin releasing factor (CRF)-immunoreactive nerve fibers and cell bodies in the spinal cord is demonstrated. Immunopositive fibers were found in the lateral column of the white matter, in laminae I, V-VII, X, and in the intermediolateral column of the spinal cord. Complete transection of the spinal cord showed that the majority of the fibers in the lateral funiculus formed an ascending pathway; however, a few descending fibers were also detected. Hypophysectomy resulted in enhanced immunoreactivity of the fibers and staining of CRF-immunoreactive cell bodies in laminae V-VII, X, and in the intermediolateral sympathetic column. The results suggest that CRF is not merely an ACTH releasing factor, but also a regulatory peptide which may be involved in several stress-related neural responses.     

大鼠下丘脑室周核内SSmRNA的表达

应用漂浮原位杂交组织化学来显示大鼠下丘脑室周核内生长抑素ｍＲＮＡ。结果表明此法具有敏感性高、背景底、实验周期短、操作简单等优点。在室周核内显示出大量的表达生长抑素ｍＲＮＡ神经元，且以室旁室周核内数量最多。     

Cell-free synthesized precursor to somatostatin-28 from the rat hypothalamus

Cell-free translation of rat hypothalamic mRNA and specific immunoprecipitation were used to identify a polypeptide of 16,000 apparent molecular weight as prepro-somatostatin. Quantifying these results suggested that the somatostatin-specific mRNA represented less than 0.01% of the total hypothalamic mRNA. Co-translational addition of microsomal membranes led to the in vitro synthesis of a pro-form of 14,500 molecular weight. By using antisera specifically recognizing 3 different but overlapping segments of somatostatin-28 (SRIF-28), the rat prepro-somatostatin was shown to contain antigenic determinants of this N-terminally extended somatostatin as well as of the tetradecapeptide (SRIF-14). Sequential immunoprecipitation experiments implied the existence of only a single somatostatin precursor among the rat hypothalamic translation products, which would have to be differentially processed to allow release of both SRIF-28 and SRIF-14.     

Neural substrates of opiate reinforcement

1. 1. A major component of opiate reward is derived from a drug action in the ventral tegmental area: (a) rats quickly learn to self-administer morphine directly into the ventral tegmentum, (b) intracranial self-administration into other brain sites is not quickly learned, and (c) narcotic antagonist microinjections into the ventral tegmentum attenuate reward from intravenous heroin infusions.

2. 2. At least one component of opiate reward is dependent on a dopaminergic system: (a) electrophysiological and neurochemical indices suggest that opiates activate ventral tegmental dopaminergic neurons, (b) ventral tegmental opiate infusions are behaviorally activating producing contralateral rotation that is blocked by neuroleptics, (c) reward from heroin is blocked by neuroleptics, and (d) reward from heroin is attenuated by dopamine-depleting lesions of the ventral tegmental system.

3. 3. Brain sites involved in the production of physical dependence on opiates are anatomically distinct from those initiating the acutely rewarding action of opiates.

4. 4. It is theoretically viable that opiates derive their reinforcing impact from a combination of positive and negative reinforcement processes: (a) the neural substrate for the positive reinforcing action probably involves a ventral tegmental dopamine system important in appetitive motivation, and (b) the neural substrate for the negative reinforcing action may involve a periventricular gray system that is independent of the system which mediates the acutely rewarding property of opiates.