Current Neurovascular Research - Volume 4, Issue 1, 2007

To investigate the effects of magnetic resonance image (MRI) exposure on CNS development, we examined the effects of neonatal exposure of rats to a MRI magnetic field on their performance in the Morris water maze. After birth, all litters were randomly divided into an MRI-scanning group (experimental group) comprised of 7 mother rats and their offspring, and a control group, which consisted of the other 7 mothers and their pups. Newborn rat pups of MRIscanning group were exposed to a 1.5 T magnetic resonance image (MRI) magnetic field for 7 days (postnatal day 1-day 7, 10 min/day). And behavioral tests were taken at 1st-, 2nd- and 5th-month after birth. At the age of 2 months postnatal, both male and female rats of the experimental groups made fewer crossings over the target area in the probe trial than did the control group. This result showed that the exposed animals represented a “reference memory” deficit, that is to say, these rats had a deficit ability to use environmental cues to locate the former position in space. No deficits were evident in the 1st- and 5th-month groups. These results demonstrate an age-specific cognitive/behavioral deficit induced by neonatal exposure to an MRI magnetic field. These findings indicate that the safety of MRI exposure must be considered with care and appropriate cautions should be taken.

This study examined whether six days recombinant human growth hormone (rhGH) affected psychological profile in an abstinent androgenic-anabolic steroid (AAS) abusing group, compared with an abstinent AAS control group. Male subjects (n = 48) were assigned in a random fashion into one of two groups: (1): (n =24) control group (C); (2): (n =24) rhGH group (GH). A hospital anxiety scale (HADS) questionnaire was completed by all subjects. Physiological responses investigated included anthropometry. Biochemical markers examined included; serum glucose, sodium, urea, lipid profile, high sensitivity C-reactive protein (hsCRP), homocysteine (HCY), tetra-iodothyronine (T4), thyroid stimulating (TSH), luteinising (LH) and follicle stimulating (FSH) hormones, testosterone (T), prolactin (PRL), cortisol and insulin like growth factor-1 (IGF-I). HADS questionnaire significantly decreased in both anxiety (A) and depression (D) symptoms within GH (P<0.017) and compared with C (P<0.05). Body mass index (BMI) and fat-free mass index (FFMI) significantly increased (both P<0.017) while body fat significantly decreased within GH (P<0.017). IGF-I significantly increased within GH (P<0.017) and significantly increased compared with C (P<0.05). Serum sodium significantly increased (P<0.017) and serum HCY, hsCRP, TSH and T4, significantly decreased within GH (all P<0.017). PRL significantly increased and T4 significantly decreased compared with C (both P<0.05). The findings of this study suggest that short term use of rhGH has beneficial effects on mental state in individuals who were previous abusers of AAS and appeared to have a beneficial effect on cardiovascular risk markers associated with adverse mental health.

The hippocampus has long been associated with learning, memory, and modulation of emotional responses. Previous studies demonstrated that stress-induced loss of hippocampal neurons may contribute to the pathogenesis of depression. The recent observations supported that antidepressant drugs increase the production of serotoninergic neurotransmitter and they play a critical role in the initiation of neurogenesis in the hippocampus. In order to explore the possible new mechanism of the treatment of depression, we cultured neural stem cells (NSCs) derived from the hippocampus of adult rats as an in vitro model to evaluate the capabilities of neuroprotection and neural differentiation in NSCs by fluoxetine (FL) treatment. Our results showed that 20 μM FL treatment can significantly increase the proliferation rate of NSCs (p<0.05), and up-regulate the mRNA and protein expressions of Bcl-2 in Day-7 FL-treated NSCs (p<0.01). Using Bcl-2 gene silencing with small interfering RNA, our data verified that FL can prevent Fas ligand-induced caspasedependent apoptosis in NSCs through the activation of Bcl-2. The in vitro observation and immunofluorescent study further demonstrated that FL treatment can stimulate the neurite development and serotoninergic differentiation of NSCs through the activation of Bcl-2. Using microdialysis with high performance liquid chromatography- electrochemical detection, the functional release of serotonin in the differentiating NSCs with FL treatment was increased and simultaneously regulated by the Bcl-2 expressions. In sum, the study results indicate that antidepressant administration can increase NSCs survival, promote the neurite development, and facilitate NSCs differentiating into the functional serotoninergic neurons via the modulation of Bcl-2 expression.

Stroke is associated with elevation of several proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-8 that are correlated with central nervous system (CNS) injury. Anti-platelet therapies are important agents in stroke management. The role of antiplatelets as anti-inflammatory agents is not known in acute stroke patients. Furthermore, their effect on induction of potential cytokines as TNF-α and IL-8 in those patients is still not clear. Thus, we herein examined the induction of TNF-α and IL-8 in acute stroke patients and examined the effects of the antiplatelets drugs aspirin, clopidogrel and dipyridamole, and piracetam in their induction. Cytokines were detected intracellularly in leukocytes from patients who had first acute ischemic stroke and from matched controls by immunocytochemistry. The results showed significant increase of spontaneously produced TNF-α and IL-8 in patients compared to control. This induction was significantly inhibited differently by each drug and dual drug agents. The data of this work suggest that antiplatelets agents may have a role in inhibition of stroke mediated proinflammatory cytokine effects, which may initiate a new aspect of the role of antiplatelets in the treatment of acute ischemic stroke.

Sepsis is often complicated by encephalopathy, neuroendocrine dysfunction and cardiovascular autonomic failure. The cause of septic brain dysfunction is not fully understood. The aim of the present study is to explore whether septic brain dysfunction in a common septic model in the rat correlates with abnormalities either of local cerebral blood flow (LCBF) of defined brain areas or of whole brain blood flow (CBF). 45 male Wistar rats (320± 13 g) were randomly assigned to a sepsis group (31 rats, cecal ligature and puncture, CLP) or a control group (14 rats, sham operation). Of these 45 rats, 16 rats were used for blood analysis; the remaining 29 rats were used for CBF/LCBF measurements. LCBF measurements were performed 24h after initial surgery using quantitative autoradiography with 4-iodo[N-methyl-14C]antipy- rine, which allows to analyze CBF on a regional/local and global basis. In 42 different brain regions bilateral optical density measurements were performed. Septic rats (vs. control) presented tachycardia (507± 37 vs. 452± 44 min-1, P<0.05), leukocytopenia (2.96± 2.37 vs. 8.83± 2.97•109•L-1, P<0.05), hypocapnia (29.3± 4.6 vs. 36.4± 3.9 mmHg, P<0.05), and higher serum lactate concentrations (5.7± 3.9 vs. 2.2± 2.0 mmol•L-1, P<0.05). LCBF of all 42 areas, as well as, CBF (116± 59 vs. 115±52 mL•100g-1•min-1, n.s.) did not differ. The results showed that severe sepsis (mortality rate of 43 %) did not induce alterations in mean CBF and LCBF. It is concluded that brain dysfunction is not reflected in changes of CBF during severe sepsis.

In this study, changes in cerebral blood flow (CBF) during acute phase after cardiopulmonary arrest (CPA) were examined in patients using stable Xenon enhanced computed tomography (Xe-CT). All patients (8) were stabilized hemodynamically within 4 hours after admission, and Xe-CT was performed immediately after restoration of spontaneous circulation (ROSC) at 8, 24, 48, 96 and 168 hours after ROSC. The progress of patients was monitored in other hospitals and clinics after discharge. Neurological outcomes were evaluated using the Glasgow outcome scale (GOS) 6 months after admission, and scores were compared against changes in CBF. Patients were grouped by prognosis. Four patients belonged to Group A (good recovery) and Group B (2 severely disabled, 2 in persistent vegetative state). The pattern of change in CBF after ROSC was found to be significantly different between Groups A and B (p <0.05). The CBF ratio relative to normal controls was higher in Group B than Group A within 48 hours after ROSC. However, at 48, 96, and 168 hours after ROSC, the opposite was observed: The CBF ratio was significantly higher in Group A than Group B (p<0.05). Based on these results, we concluded that CBF in the patients who survived after CPA changed remarkable especially within the first week. Furthermore, patients with abnormally low CBF that returns to supernormal within the first 48 hours following CPA can be expected to recover well neurologically.

Increased mortality due to cardiovascular disease has been described in adult patients with untreated growth hormone (GH) deficiency. GH replacement therapy has been demonstrate to improve vascular reactivity and reverses early atherosclerotic changes in GH deficient adults. The objective of this study was the assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GH deficiency and with GH replacement therapy. We studied 20 GH deficient patients, 10 men and 10 women (aged, 43.4 ± 8.4 years) under GH replacement therapy compared with a control group matched for age and body mass index, 9 men and 16 women. All subjects, patients and controls, were life-long non-smokers, normotensive and non-diabetic. The following variables were recorded: anthropometrical and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin fragments and fibrin degradation product D-dimer that were determined by an enzymelinked- immunosorbent assay (ELISA); IGF-I by radioimmunoassay; C-reactive protein by highly sensitive immunonephelometry; E-selectine, P-selectine, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6 and monocyte chemoattractant protein-1 by ELISA. The assessment of endothelial function in vivo was measured by Doppler. Patients with GH deficiency had higher hip/waist ratio and C-peptide and triglycerides concentrations than controls. Our results demonstrated no difference in fibrinolytic markers among patients and controls. E-selectin concentrations were higher in patients than in controls, 22.5± 11.4 vs. 10.7± 6.2 μg/L, p= 0.0001. P-selectin, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1 and C-reactive protein were similar in the 2 groups. Vascular reactivity and carotid intimamedia thickness were also similar in patients and controls. In this study we have demonstrated in adults with GH deficiency under GH substitution elevation of E-selectin concentrations that may correlate with potential endothelial dysfunction suggesting that the protective effect of GH in these patients may be enhancing other mechanisms.

Diabetes mellitus (DM) affects approximately 170 million individuals worldwide and is expected to alter the lives of at least 366 million individuals within a future span of 25 years. Of even greater concern is the premise that these projections are underestimated since they assume obesity levels will remain constant. Type 1 insulin-dependent DM accounts for only 5-10 percent of all diabetics but represents a highly significant health concern, since this disorder begins early in life and leads to long-term complications. In contrast, Type 2 DM is recognized as the etiology of over 80 percent of all diabetics and is dramatically increasing in incidence as a result of changes in human behavior and increased body mass index. Yet, the pathological consequences of these disorders that involve the both the neuronal and vascular systems are intimately linked through the pathways that mediate oxidative stress. Here we highlight some of the relevant oxidative pathways that determine insulin resistance through reactive oxygen species, mitochondrial dysfunction, uncoupling proteins, and endoplasmic reticulum stress. These pathways are ultimately linked to protein kinase B (Akt) and the insulin signaling pathways that determine the initial onset of glucose intolerance and the subsequent course to apoptotic cell injury. Through the elucidation of these targets, improvement in current strategies as well as the development of future clinical applications can move forward for both the prevention and treatment of Type 1 and Type 2 DM.