The blood-brain barrier: an overview: structure, regulation, and clinical implications.

The chronic mild stress (CMS) model of depression has high validity but has in the past been criticized for being difficult to replicate. However, a large number of recent publications have confirmed

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Resistance exercise has been shown to elicit a significant acute hormonal response. It appears that this acute response is more critical to tissue growth and remodelling than chronic changes in resting hormonal concentrations, as many studies have not shown a significant change during resistance training despite increases in muscle strength and hypertrophy. Anabolic hormones such as testosterone and the superfamily of growth hormones (GH) have been shown to be elevated during 15-30 minutes of post-resistance exercise providing an adequate stimulus is present. Protocols high in volume, moderate to high in intensity, using short rest intervals and stressing a large muscle mass, tend to produce the greatest acute hormonal elevations (e.g. testosterone, GH and the catabolic hormone cortisol) compared with low-volume, high-intensity protocols using long rest intervals. Other anabolic hormones such as insulin and insulin-like growth factor-1 (IGF-1) are critical to skeletal muscle growth. Insulin is regulated by blood glucose and amino acid levels. However, circulating IGF-1 elevations have been reported following resistance exercise presumably in response to GH-stimulated hepatic secretion. Recent evidence indicates that muscle isoforms of IGF-1 may play a substantial role in tissue remodelling via up-regulation by mechanical signalling (i.e. increased gene expression resulting from stretch and tension to the muscle cytoskeleton leading to greater protein synthesis rates). Acute elevations in catecholamines are critical to optimal force production and energy liberation during resistance exercise. More recent research has shown the importance of acute hormonal elevations and mechanical stimuli for subsequent up- and down-regulation of cytoplasmic steroid receptors needed to mediate the hormonal effects. Other factors such as nutrition, overtraining, detraining and circadian patterns of hormone secretion are critical to examining the hormonal responses and adaptations to resistance training.

Hormonal Responses and Adaptations to Resistance Exercise and Training

The blood–brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFβ, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain endothelial permeability has been shown for a number of small chemical mediators produced by astrocytes and other nearby cell types. It is clear that endothelial cells are involved in both long- and short-term chemical communication with neighbouring cells, with the perivascular end feet of astrocytes being of particular importance. The role of barrier induction and modulation in normal physiology and in pathology is discussed.

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Astrocyte–endothelial interactions and blood–brain barrier permeability*

Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

/pdf/stressor-specificity-of-central-neuroendocrine-responses-3hrslqz38s.pdf

Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes

The effect of feed restriction on plasma hormones (triiodothyronine — T3, thyroxine — T4, and corticosterone), protein, lipid, carbohydrate, and mineral metabolism and activity of plasma enzymes (creatine kinase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) were studied in meat type female chickens (Gallus gallus). Ad libitum fed birds were compared with those subjected to severe and moderate quantitative feed restriction from 16 to 100 days of age. Feed restriction elevated plasma T4 and corticosterone levels and reduced T3. A feed restriction-induced decrease was observed for plasma protein and albumin concentrations, but not for uric acid and creatinine. Total plasma lipids, triacylglycerols, cholesterol, high density lipids, and calcium were lower for the feed restricted chickens, in particular during the latter phase of the experiment. Concentrations of glucose and phosphorus were not altered by feeding treatment. Activity of alkaline phosphatase was significantly increased in restricted chicks from day 58. Significant changes of plasma biochemical parameters induced by severe and moderate quantitative feed restriction illustrate that limiting feed intake poses an intensive stress on meat type chickens during the rapid growth period. However, activities of creatine kinase, aspartate aminotransferase, and alanine aminotransferase were significantly higher in ad libitum fed chickens during this period. This elevation in enzymatic activity may be in response to tissue damage, indicating potential health and welfare problems also in ad libitum fed meat type chickens, resulting from selection for intensive growth.

The effects of feed restriction on plasma biochemistry in growing meat type chickens (Gallus gallus).

Stress-induced increase in blood-brain barrier permeability in control and monosodium glutamate-treated rats

The dynamic patterns of pituitary-adrenocortical and sympatho-adrenal hormone responses to insulin hypoglycemia as well as the relative importance of central vs. peripheral control of hypoglycemia-induced ACTH secretion were evaluated. In conscious rats bearing indwelling cannulae, the changes in hormone concentrations after insulin injection were dependent on the changes in blood glucose levels with respect to both time course and magnitude. ACTH, corticosterone, epinephrine, and norepinephrine levels were found to be maximal at 60 min after 2.5 IU kg-1 insulin injected ip, whereas earlier (20 min) but smaller increases were obtained in response to 0.5 IU kg-1 insulin injected iv. In rats 6-7 days after lesions of the medial basal hypothalamus (MBH), the rise of ACTH during insulin hypoglycemia was markedly inhibited and corticosterone levels were significantly reduced. Simultaneously, the hypoglycemia-induced increase in plasma epinephrine was unchanged and that in plasma norepinephrine was significantly enhanced in rats with the MBH destroyed. The beta-adrenoreceptor blocker propranolol did not inhibit ACTH and corticosterone responses to hypoglycemia in either sham-operated or MBH-lesioned animals. We conclude that the main factors triggering ACTH release during insulin-induced hypoglycemia are of central rather than peripheral origin. The high concentrations of circulating catecholamines occurring during insulin hypoglycemia are not responsible for pituitary-adrenocortical activation by direct, beta-adrenoreceptor mediated action at the pituitary level.

Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms.

The effects of pharmacological stimulation or blockade of adrenergic receptors on plasma testosterone levels were studied in healthy men subjected to bicycle ergometer exercise. Plasma testosterone in

Daniela Ježová

Papers

Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes

The effects of feed restriction on plasma biochemistry in growing meat type chickens (Gallus gallus).

Stress-induced increase in blood-brain barrier permeability in control and monosodium glutamate-treated rats

Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms.

Testosterone Response to Exercise during Blockade and Stimulation of Adrenergic Receptors in Man