Current Neurovascular Research - Volume 5, Issue 4, 2008

Major depression is a common, serious and recurrent disorder that affects 17-20% of the population of the world. The chronic mild stress (CMS) model has been used as an animal model of depression but reflect anhedonia in animals. Present study investigated behavioral, physiological and neurochemical aspects of rats exposed to a CMS procedure. The consumption of sweet food, locomotor activity, body and adrenal gland weight, BDNF protein levels evaluated in hippocampus, cerebrospinal fluid and serum were assessed in rats. Our findings demonstrated decreased in sweet food intake, increase of adrenal gland weight and a decrease of body weight and no changes were observed in BDNF protein levels in serum, cerebrospinal fluid and hippocampus in rats subjected to CMS procedure. Indeed, locomotor activity was not significantly affected. In conclusion, these data reveal that BDNF protein levels were not significantly correlated with the decrease of sweet food consumption observed in CMS exposed animals.

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia. To test this hypothesis, marginal periodontitis was induced by ligatures on the second maxillary molars in BB/LL Wistar rats for 3 weeks. Two weeks after periodontitis initiation, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery. After a survival time of 7 days after ischemia, rats were killed and bone loss was determined on the buccal and palatinal surfaces of the defleshed jaw. In addition, markers of systemic inflammation were determined in a different group of laboratory animals at 14 days after the onset of periodontitis. The infarct size and markers of the inflammatory reaction in the brain were determined by immunohistochemistry. We found: (i) rats with ligatures exhibited significantly more periodontal bone loss than the control rats; (ii) the development of periodontitis was associated with an elevated gene expression for several markers of systemic inflammation (interleukin-10, transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-1beta and interferon gamma; (iii) rats with periodontitis and a mild systemic inflammation had a significantly reduced infarct volume and a significant reduction in the number of brain macrophages in the infarcted area. In conclusion we found that mild systemic inflammation elicited prior to stroke onset may have a neuroprotective effect in rats by reducing the infarct volume and tissue destruction by brain macrophages.

Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS. Several clinical studies have attempted to elucidate the role of gender hormones in the evolution of the clinical spectrum of the disease. We attempt to describe the currently known data regarding such associations emphasizing the potential clinical applications in different MS scenarios i.e. pregnancy, menstruation, use of oral contraceptives and hormonal replacement therapy. Moreover we discuss relevant effects of gender hormones on immunological parameters relating to MS pathogenesis. Beneficial neuroprotective effects were noted for elevated levels of estrogens, progesterone and elevated dosages of androgens. Some of these changes may be explained by a favorable immunological shift from a Th1 to Th2 response. Further elucidation of the clinical implications of such associations is necessary.

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) were originally identified as endothelial-specific ligands regulating key functions of the vasculature important in stroke. There is increasing evidence that these ligands also exert effects on neurons. Here we review the neuronal effects of VEGF and Ang1 and highlight their potential for therapeutic manipulation in stroke. VEGF stimulates angiogenesis whereas Ang1 suppresses leakage, inflammation and regression of microvessels. Expression of both ligands change dramatically in the brain in experimental stroke, correlating with increased vascular leakage and inflammation. In addition to vascular effects, VEGF can stimulate survival, migration and proliferation of neurons suggesting roles in neural protection and possible therapeutic applications, an idea supported by preclinical studies. Recent reports now demonstrate that Ang1 can also act directly on neurons and enhance neural repair. The realization that VEGF and Ang1 have effects on both neural and vascular compartments impacted by stroke provides new opportunities for therapeutic manipulation to promote neuroprotection and extend the thrombolytic window, as well as stimulating neurogenesis and revascularization.

Vascular Endothelial Growth Factor (VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration. Findings of neuropilins as shared co-receptors between molecules with such seemingly different functions as the axon guidance molecules semaphorins and VEGF has further boosted the interest in the role of VEGF in neural tissue injury and repair mechanisms. Thus, VEGF most likely act in parallel or concurrent on cells in both the vascular and nervous system. The present review gives a summary of known or potential aspects of the VEGF system in the healthy and diseased nervous system. The potential benefits but also problems and pitfalls in intervening in the actions of such a multifunctional factor as VEGF in the disordered CNS are also covered.

Physiologic functioning of the cerebrovenous system is indispensable for maintaining normal brain function. However, in contrast to the cerebroarterial system, the cerebral venous return is not routinely investigated. Combined high-resolution echo-colour-Doppler (ECD) and transcranial colour coded Doppler sonography (TCCS) represents an ideal method to investigate the haemodynamics of cerebral venous return. TCCS-ECD is noninvasive, repeatable, costeffective and permits to investigate the cerebral venous outflow in its dependence upon changes in posture and the alternating pressure gradients of the thoracic pump. Several authors reported normal parameters concerning related aspects of cerebral venous return. However, there is no ECD-TCCS standardization of what can be considered a normal venous return. The authors have summarized the current knowledge of the Doppler haemodynamics of the cerebrovenous system and propose a list of reproducible clinical parameters for its sonographic evaluation. In future, the development of this diagnostic technique could be of singular interest in iron-related inflammatory and neurodegenerative disorders like multiple sclerosis.

Alcohol one of the important products of the global addiction alters brain function by interacting with multiple neurotransmitter systems, thereby disrupting the delicate balance between inhibitory and excitatory neurotransmitters. Alcohol positively reinforces drinking by producing a mild euphoria. The reinforcing effects of alcohol are mediated by several neurochemical systems and are associated with some of the behavioral manifestations of intoxication. Alcohol consumption is initially accompanied by decreased attention, alterations in memory, mood changes and drowsiness. Generally all vital functions of brain depend on a delicate balance between excitatory and inhibitory neurotransmission, which in turn dependent on short and long term alcohol consumption. Detailed understanding of alcohol's mechanism of action on the neurotransmitters of brain is a prerequisite in discovering effective treatments for both alcohol abuse and alcoholism. This review covers the elaborate literature on the subject, and highlights the functions and interactions of neurotransmitters and alcoholism.