The Neuroprotective Effects of Semax in Conditions of MPTP-Induced Lesions of the Brain Dopaminergic System

This report describes studies cf the effects of the ACTH(4-10) analog Semax (MEHFPGP) on the behavior of white rats with lesions to the brain dopaminergic system induced by the neurotoxin MPTP. Neurotoxin was given as single i.p. doses of 25 mg/kg. Neurotoxin injections were shown to decrease movement activity and increase anxiety in the animals. Daily intranasal administration of Semax at a dose of 0.2 mg/kg decreased the severity of MPTP-induced behavioral disturbances. The protective activity of Semax in MPTP-induced lesions of the brain dopaminergic system may be associated with both its modulating effect on the dopaminergic system and the neurotrophic action of the peptide.     

The Role of Glucocorticoid Hormones in the Stress-Protective Effects of Hypoxic Postconditioning in Models of Depression and Post-Traumatic Stress Disorder in Rats

Neuroscience and Behavioral Physiology - The effects of using neuroprotective hypoxic hypobaric postconditioning (PostC) were studied in two experimental models: stress-restress post-traumatic...     

Structural Changes in Mesocorticolimbic Dopaminergic System of the Brain during Long-Term Alcoholization in Rats

We studied morphofunctional changes in structures of the mesocorticolimbic system of rat brain upon long-term (5 months) ethanol intoxication. Alcoholization reduced the volume and specific density of neurons in the substantia nigra and ventral tegmental area. The density of neurogliocytes in the substantia nigra and ventral tegmental area increased. Neuronal density in the nucleus accumbens and anterior cingulate cortex significantly decreased, the volume of viable neurons slightly increased. One month after alcohol cessation, the volume of neurons in the substantia nigra and ventral tegmental area remained elevated against the background of their reduced density. The density of neuroglia in the nucleus accumbens and anterior cingulate cortex remained at the level observed during alcoholization. Significant decrease in the density and decrease in the volume of neurons in structures of the mesocorticolimbic system accompanied by the increase in neuroglyocyte density in these structures can be considered as morphological signs of long-term alcoholic intoxication, which persist after alcohol cessation. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 698-700, December, 2008     

The Dopaminergic System of the Telencephalo-Diencephalic Areas of the Vertebrate Brain in the Organization of the Sleep–Waking Cycle

The aim of the present work was to study the involvement of the dopaminergic system of the telencephalic and diencephalic areas of the vertebrate brain in the organization of the sleep–waking cycle in cold-blooded and warm-blooded vertebrates. Immunohistochemical studies of tyrosine hydroxylase content, this being the key enzyme in dopamine synthesis, in the striatum, supraoptic and arcuate nuclei, and zona incerta of the hypothalamus of sturgeon and mammals (rats) of three age groups (14 and 30 days and adults), in conditions of tactile and sleep-deprivation stressors. In fish, transient stress was followed by the detection of tyrosine hydroxylase-immunoreactive cells in all parts of the brain. In prolonged stress, tyrosine hydroxylase-immunoreactive cells and fibers were not found in the forebrain, though they were well represented in the hypothalamic nuclei. In 14-day-old rat pups, 2-h sleep deprivation increased the tyrosine hydroxylase content of fibers in the caudate nucleus and cells in the zona incerta of the hypothalamus, while 30-day-old animals subjected to 6-h sleep deprivation showed increases in tyrosine hydroxylaseimmunoreactive material contents in cells in the paraventricular nucleus and decreases in the quantity in fibers. In adult rats, the arcuate nucleus and zona incerta showed decreases in the content of tyrosine hydroxylase-immunoreactive material on the background of sleep deprivation, with increases during postdeprivation sleep. These data are discussed in the light of the phylo- and ontogenetic development of the neurosecretory and neurotransmitter functions of the dopaminergic system in the evolutionarily ancient diencephalic and evolutionarily young telencephalic areas of the vertebrate brain as major systems triggering and maintaining the functional states of the body during the sleep–waking cycle.     

Effects of Genetic Variations in the Dopaminergic System on Fatigue in Humans: Gender Aspects

Changes in the functional status under the effect of intense mental exercise were studied in carriers of different variants of DAT1, DRD2, and COMT genes. The volunteers (n=140) performed 3-h monotonous mental work (information processing and logical problem solving). The degree of fatigue was evaluated before and after exercise by the HAM (Health status– Activity–Moods) and AMF (Acute Mental Fatigue) questionnaires. A signifi cant relationship between the DAT1, DRD2, and COMT gene polymorphism and changes in the mental sphere status were revealed. The effects of these polymorphisms were the most pronounced in girls. The results are discussed within the framework of hypothesis on the effects of changes in the phasic/tonic dopamine proportion on the studied functions.     

P38、MAPK-1和AQP-4在糖皮质激素调节大鼠创伤性脑水肿中的作用

目的 探讨糖皮质激素对P38、丝裂原活化蛋白激酶（MAPK-1）的调节作用及其对大鼠创伤后脑组织水通道蛋白 4（AQP-4）表达的影响。方法 选择SPF级雄性SD大鼠140只,随机分为假手术组、模型组、低剂量治疗和高剂量治疗组,各35只。假手术组单纯实施开颅手术,模型组、低剂量治疗组和高剂量治疗组用Feeney's自由落体法制备大鼠脑创伤模型,高剂量治疗组和低剂量治疗组分别予高、低甲泼尼龙尾静脉注射。分别于伤后0、6、24、72 h、7 d处死动物,取脑组织标本,透射电镜观察各组大鼠神经细胞结构变化,免疫组化法测定各组大鼠AQP-4、P38、MAPK-1的表达水平,用荧光探针原位杂交法测定AQP-4mRNA的表达。结果 ①假手术组大鼠脑神经结构基本正常,细胞质、细胞膜及细胞核完整清晰。模型组神经细胞体积缩小,细胞膜结构破坏,胞浆疏松,细胞核固缩,凋亡小体形成。与模型组相比,低剂量治疗组、高剂量治疗组大鼠神经细胞坏死程度均较轻。②低剂量治疗组及高剂量治疗组大鼠伤后24、72 h及7 d的AQP-4阳性表达率均低于模型组,差异有统计学意义（P＜0.05）,低剂量与高剂量治疗组间表达比较,差异无统计学意义（P＞0.05）。低剂量治疗组及高剂量治疗组大鼠在伤后24、72 h及7 d的P38、MAPK-1阳性表达率均低于模型组,差异有统计学意义（P＜0.05）,低剂量与高剂量治疗组间比较,差异无统计学意义（P＞0.05）。③低剂量治疗组和高剂量治疗组的AQP-4mRNA阳性表达率在伤后24、72 h及7 d均低于模型组,高于假手术组,差异有统计学意义（P＜0.05）;低剂量与高剂量治疗组间比较,差异无统计学意义（P＞0.05）。结论 糖皮质激素可以降低大鼠创伤后脑组织AQP-4 的表达及脑损伤,其作用机制可能与抑制P38、MAKP-1激活、降低下游 AQP-4 的表达有关。     

胃肠激素在记忆调节中的作用研究进展

脑-肠轴,即脑与胃肠激素之间的相互作用关系已研究多年。脑-肠轴是一种双向的信息交流,它不但调节了胃肠功能的稳态而且与更高级的情绪与认知功能相关。进食时,消化道会分泌很多激素并通过外周途径影响不同的组织器官,包括大脑。而下丘脑在能量代谢、营养平衡以及摄食行为调控中起到重要的作用,它能将内脏功能与海马、杏仁核及皮层等肢体功能进一步整合起来。这些脑区主要参与大脑的高级功能,如认知功能、及情绪的调节。现对近年来不同胃肠激素对学习与记忆的调节功能进行综述。了解这类激素在记忆中的作用,将有助于寻找治疗与学习记忆障碍相关神经疾病的新型治疗策略。     

Involvement of the Mesocorticolimbic Dopaminergic System in Adaptive Behavior

The midbrain dopaminergic system is traditionally regarded as a “common neural currency” for rewards of any modality. As regards the specific involvement of the mesocorticolimbic system in behavior there are currently three main hypotheses under consideration: 1) dopamine mediates “satisfaction;” 2) dopamine signals errors in predictions of rewards and thus serves as a learning signal critical in processes of associative learning; 3) dopamine creates motivation for actions directed to receiving a reward. However, considerable evidence has been obtained providing different levels of contradiction of these views of the functions of central dopamine. Attempts to clarify the role of the mesocorticolimbic dopaminergic system in adaptive behavior have shown that this system is involved in learning processes, in assessing the results of actions, in the processes identifying the significance of new stimuli, and in the mechanisms of decision-taking, though most studies have provided evidence that that the activity of the mesocorticolimbic system is of particular importance in situations of indeterminacy. We believe that this is the major enigma of dopamine, on the one hand supporting spontaneity and, on the other, protecting against excessive reactivity.     

The Role of the Immune System in Clearance of Aβ from the Brain

In Alzheimer's disease (AD), there is abnormal accumulation of Aβ and tau proteins in the brain. There is an associated immunological response, but it is still unclear whether this is beneficial or harmful. Inflammation in AD, specifically in the form of microglial activation, has, for many years, been considered to contribute to disease progression. However, two types of evidence suggest that it may be appropriate to revise this view: first, the disappointing results of prospective clinical trials of anti-inflammatory agents and, second, the observation that microglia can clear plaques in AD following Aβ immunization. Although Aβ immunization alters AD pathology, there is limited evidence so far of benefit to cognitive function. Immunization against microorganisms is almost always used as a method of disease prevention rather than to treat a disease process that has already started. In animal models, immunotherapy at an early age can protect against Aβ accumulation and it will be interesting to see if this can usefully be applied to humans to prevent AD.     

急性脑缺血家兔神经肽激素的观察

１７只家兔分为两组，９只夹闭双侧颈总动脉，造成急性脑缺血，８只作正常对照。两组取下丘脑和血浆均作精氨酸加压素（ＡＶＰ）、β－内啡肽（β－ＥＰ）和ｃＡＭＰ测定。急性脑缺血时下丘脑和血浆中ＡＶＰ、β－ＥＰ升高，而ｃＡＭＰ降低。提示神经肽激素在急性脑缺血中起重要作用。     

Studies on the Immunosuppressive Role of Steroid Hormones During Pregnancy

It has been recognised that steroids can exert a profound influence over immunological reactivity. The present study analyzes the role of steroid hormones -estrogen, progesterone and cortisol - and their involvement in immunoregulation during pregnancy. As is known, the endogenous levels of all the three hormones increase during pregnancy. When the steroid levels in pregnancy serum were correlated with the lymphocyte response to mitogen, no correlation was observed. The suppressive effect of pregnancy serum was found to have no correlation with its steroid content. In general, steroids did not seem to affect the maternal immune system as evidenced by the present study.     

Contribution of Glucocorticoid Hormones to the Gastroprotective Effect of Ischemic Preconditioning in Rats in Normal Conditions and In Prostaglandin Deficiency

The aim of the present work was to study the contribution of glucocorticoid hormones to the gastroprotective effects of ischemic preconditioning in a gastric ischemia/reperfusion model in rats with normal and deficient prostaglandin production. The contribution of glucocorticoids was evaluated by adrenalectomy followed by corticosterone replacement therapy and transient inhibition of corticosterone synthesis with metyrapone. Prostaglandin synthesis was blocked with indomethacin. Gastric ischemia was created by compression of the celiac artery in anesthetized rats. Ischemic preconditioning (0.5 h ischemia/reperfusion) stimulated corticosterone production and decreased the formation of gastric erosions due to 3.5 h ischemia/reperfusion. Adrenalectomy and administration of metyrapone prevented the gastroprotective effect of ischemic preconditioning on the backgrounds of both normal and deficient prostaglandin production. Corticosterone replacement therapy restored the effect of ischemic preconditioning in adrenalectomized rats, even in conditions of blockade of prostaglandin synthesis. Thus, glucocorticoid hormones make a contribution to the gastroprotective effect of ischemic preconditioning in conditions of normal prostaglandin production, as well as in conditions of blockade of prostaglandin synthesis.     

Role of Thyroid Hormones in Stress-Induced Synthesis of Heat-Shock Proteins in the Myocardium

Thyroxine in near-physiological doses increased the content of heat-shock proteins in the myocardium and stimulated their accumulation during immobilization stress. Blockade of thyroid functions with methimazole decreased the content of heat-shock proteins in rat myocardium during stress and heat shock and prevented their accumulation during adaptation to short-term immobilizations.     

Role of Adipokines and Hormones of Obesity in Childhood Asthma

Purpose

The aim of this study was to evaluate serum levels of leptin, ghrelin, and adiponectin in obese and non-obese children with asthma and in healthy non-asthmatic children, and analyze their relationships with clinical outcomes.

Methods

This study enrolled 40 obese and 51 non-obese children with asthma and 20 healthy children. Body mass index and serum leptin, ghrelin, and adiponectin levels were determined in all children. Asthma symptom scores and lung function test results were recorded for subjects with asthma.

Results

Serum leptin levels (11.8±7.9, 5.3±6.8, and 2.1±2.4 ng/mL in the obese asthmatic, non-obese asthmatic, and control groups, respectively) and adiponectin levels (12,586.2±3,724.1; 18,089.3±6,452.3; and 20,297.5±3,680.7 ng/mL, respectively) differed significantly among the groups (P<0.001 for all). Mean ghrelin levels were 196.1±96.8 and 311.9±352.8 pg/mL in the obese and non-obese asthmatic groups, respectively, and 348.8±146.4 pg/mL in the control group (P=0.001). The asthma symptom score was significantly higher in the obese children with asthma than in the non-obese children with asthma (P<0.001). Leptin and adiponectin levels were correlated with the asthma symptom score in non-obese children with asthma (r=0.34 and r=-0.62, respectively).

Conclusions

Obesity leads to more severe asthma symptoms in children. Moreover, leptin, adiponectin, and ghrelin may play important roles in the inflammatory pathogenesis of asthma and obesity co-morbidity.     

Experimental Modeling of Functional Deficiency of the Nigrostriatal Dopaminergic System in Mice

The dopaminergic nigrostriatal system of the brain is a key component in controlling motor behavior. The bodies of dopaminergic neurons are located in the compact zone of the substantia nigra and their axons, forming the nigrostriatal tract, project to the striatum. The aim of the present work was to develop an experimental model of functional deficiency of the dopaminergic neurons of the nigrostriatal system with no impairment to motor behavior, i.e., the presymptomatic stage of parkinsonism. The model was created in mice by administration of single subcutaneous injections of low doses (12 mg/kg) of 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is converted to MPP⁺ in the brain, this being a neurotoxin for dopaminergic neurons. These experiments showed that 14 days after administration of MPTP the animals a) lacked any impairment to motor behavior; b) had no decrease in the dopamine level or any dopamine neuron degeneration in the substantia nigra; c) showed significant reductions in dopamine levels in the striatum due to degeneration of half of its dopaminergic fibers. The absence of changes in motor behavior in the presence of significant changes in dopamine metabolism and structural damage to dopaminergic axons in the striatum provides evidence for the activation of compensatory mechanisms in the brain. Thus, we have developed an experimental model of the presymptomatic stage of parkinsonism, which is characterized by degeneration of the axons of dopaminergic neurons in the striatum with no changes in the bodies of these neurons in the substantia nigra; this model will be used for further studies of compensatory mechanisms.     

Role of Palliative Radiotherapy in Brain Metastases

Background:

Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases.

AIM:

The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status.

Materials and Methods:

This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale.

Results:

Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study.

Conclusion:

External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.