| Current
Neurovascular Research
ISSN: 1567-2026
Current Neurovascular Research
Volume 4, Number 1, February 2007
Contents
Age-Specific Impairment of Morris Water Maze Performance Following
Neonatal Exposure to Magnetic Resonance Image in Rats
Pp. 1-7
L. Yang, Y.-M. Guo, T.-Z. Han, K. Meng and W. Xie
[Abstract] [Full
text article]
Recombinant Human Growth Hormone in Abstinent
Androgenic Anabolic Steroid Use: Psychological, Endocrine
and Trophic Factor Effects Pp. 9-18
M.R. Graham, B. Davies, A. Kicman, D. Cowan, D. Hullin
and J.S. Baker
[Abstract] [Full
text article]
Antidepressant Administration Modulates Neural Stem
Cell Survival and Serotoninergic Differentiation Through Bcl-2
Pp. 19-29
S.-J. Chen, C.-L. Kao, Y.-L. Chang, C.-J. Yen, J.-W. Shui,
C.-S. Chien, I.-L. Chen, T.-H. Tsai, H.-H. Ku and S.-H. Chiou
[Abstract] [Full
text article]
TNF-α
and IL-8 in Acute Stroke and the Modulation of these Cytokines
by Antiplatelet Agents Pp. 31-37
A. Al-Bahrani, S. Taha, H. Shaath and M. Bakhiet
[Abstract] [Full
text article]
Local Cerebral Blood Flow is Preserved in Sepsis
Pp. 39-47
J. Hinkelbein, H. Schroeck, A. Peterka, C. Schubert, W.
Kuschinsky and A. Kalenka
[Abstract] [Full
text article]
Acute Cerebral Blood Flow Variations after Human Cardiac
Arrest Assessed by Stable Xenon Enhanced Computed Tomography
Pp. 49-54
Y. Inoue, T. Shiozaki, T. Irisawa, T. Mohri, K. Yoshiya,
H. Ikegawa, O. Tasaki, H. Tanaka, T. Shimazu and H. Sugimoto
[Abstract] [Full
text article]
Elevation of E-Selectin Concentrations may Correlate
with Potential Endothelial Dysfunction in Individuals with
Hypopituitarism During Therapy with Growth Hormone
Pp. 55-62
J.M. Gómez, M. Sahún, R. Vila, P. Domènech,
P. Catalina, J. Soler and L. Badimón
[Abstract] [Full
text article]
REVIEW ARTICLE
Oxidative Stress Biology and Cell Injury During Type
1 and Type 2 Diabetes Mellitus Pp. 63-71
K. Maiese, S.D. Morhan and Z.Z. Chong
[Abstract] [Full
text article]
Abstracts
[Back to top]
Age-Specific Impairment of Morris Water Maze Performance Following
Neonatal Exposure to Magnetic Resonance Image in Rats
L. Yang, Y.-M. Guo, T.-Z. Han, K. Meng and W. Xie
[Full
text article]
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 MRI-scanning 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.
[Back to top]
Recombinant Human Growth Hormone in Abstinent
Androgenic Anabolic Steroid Use: Psychological, Endocrine
and Trophic Factor Effects
M.R. Graham, B. Davies, A. Kicman, D. Cowan, D. Hullin
and J.S. Baker
[Full
text article]
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) sig-nificantly
increased (both P<0.017) while body fat significantly
decreased within GH (P<0.017).
IGF-I significantly in-creased 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.
[Back to top]
Antidepressant Administration Modulates Neural Stem
Cell Survival and Serotoninergic Differentiation Through Bcl-2
S.-J. Chen, C.-L. Kao, Y.-L. Chang, C.-J. Yen, J.-W. Shui,
C.-S. Chien, I.-L. Chen, T.-H. Tsai, H.-H. Ku and S.-H. Chiou
[Full
text article]
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 caspase-dependent
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.
[Back to top]
TNF-α
and IL-8 in Acute Stroke and the Modulation of these Cytokines
by Antiplatelet Agents
A. Al-Bahrani, S. Taha, H. Shaath and M. Bakhiet
[Full
text article]
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.
[Back to top]
Local Cerebral Blood Flow is Preserved in Sepsis
J. Hinkelbein, H. Schroeck, A. Peterka, C. Schubert, W.
Kuschinsky and A. Kalenka
[Full
text article]
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]antipyrine, 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.
[Back to top]
Acute Cerebral Blood Flow Variations after Human Cardiac
Arrest Assessed by Stable Xenon Enhanced Computed Tomography
Y. Inoue, T. Shiozaki, T. Irisawa, T. Mohri, K. Yoshiya,
H. Ikegawa, O. Tasaki, H. Tanaka, T. Shimazu and H. Sugimoto
[Full
text article]
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.
[Back to top]
Elevation of E-Selectin Concentrations may Correlate
with Potential Endothelial Dysfunction in Individuals with
Hypopituitarism During Therapy with Growth Hormone
J.M. Gómez, M. Sahún, R. Vila, P. Domènech,
P. Catalina, J. Soler and L. Badimón
[Full
text article]
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 enzyme-linked-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.
[Back to top]
Oxidative Stress Biology and Cell Injury During Type
1 and Type 2 Diabetes Mellitus Pp. 63-71
K. Maiese, S.D. Morhan and Z.Z. Chong
[Full
text article]
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.
|
