|
Current
Neurovascular Research
ISSN: 1567-2026
Current Neurovascular Research
Volume 5, Number 2, May 2008
Contents
ORIGINAL ARTICLES
Induction of Nuclear Receptors and Drug Resistance in the
Brain Microvascular Endothelial Cells Treated with Antiepileptic
Drugs Pp. 82-92
L. Lombardo, R. Pellitteri, M. Balazy and V. Cardile
[Abstract]
A SELDI-TOF-MS Study in Lacunar Stroke with Subsequent
Haptoglobin Phenotyping Pp. 93-98
J. Staals, J.A.P. Bons, R.J. van Oostenbrugge,
I.L.H. Knottnerus, M.P. van Dieijen-Visser, F.G. Bouwman,
E.C. Mariman, J.R. Delanghe, J. Lodder and W.K.W.H.
Wodzig
[Abstract]
Gastrin-Releasing Peptide Receptors Regulate Proliferation
of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase
Dependent Mechanism Pp. 99-105
D.G. Flores, C.B. de Farias, J. Leites, M.S.
de Oliveira, R.C. Lima, A.S.K. Tamajusuku, L.P. Di Leone,
L. Meurer, A.L. Brunetto,G. Schwartsmann, G. Lenz and
R. Roesler
[Abstract]
Association of Soluble Adhesion Molecule and C-Reactive
Protein Levels with Silent Brain Infarction in Patients with
and Without Type 2 Diabetes 106-111
T. Umemura, T. Kawamura, T. Sakakibara, A. Kanai,
T. Sano, N. Hotta and G. Sobue
[Abstract]
Gelatin-Siloxane Hybrid Scaffolds with Vascular
Endothelial Growth Factor Induces Brain Tissue Regeneration
Pp. 112-117
H. Zhang, T. Kamiya, T. Hayashi, K. Tsuru, K.
Deguchi, V. Lukic, A. Tsuchiya, T. Yamashita, S. Hayakawa,
Y. Ikeda, A. Osaka and K. Abe
[Abstract]
MIP-1α
and MCP-1 Induce Migration of Human Umbilical Cord
Blood Cells in Models of Stroke Pp. 118-124
L. Jiang, M. Newman, S. Saporta, N. Chen, C. Sanberg, P.R.
Sanberg and A.E. Willing
[Abstract]
REVIEW ARTICLES
Erythropoietin and Oxidative Stress Pp. 125-142
K. Maiese, Z.Z. Chong, J. Hou and Y.C. Shang
[Abstract]
HspB5/αB-Crystallin:
Properties and Current Progress in Neuropathy Pp.
143-152
Z. Hu and T. Li
[Abstract]
Abstracts
[Back to top]
Induction of Nuclear Receptors and Drug Resistance
in the Brain Microvascular Endothelial Cells Treated with
Antiepileptic Drugs
L. Lombardo, R. Pellitteri, M. Balazy and V. Cardile
Our work contributes to the understanding of the mechanisms
of drug resistance in epilepsis. This study aimed to investigate
i) the levels of expression of P-glycoprotein (P-gp), and
multidrug resistance-associated proteins (MRP)1 and 2, ii)
the activation of the pregnane X receptor (PXR) and the constitutive
androstane receptor (CAR), and iii) the relationship between
increased P-gp and MRPs expression and PXR and CAR activation,
in immortalized rat brain microvascular endothelial cell lines,
GPNT and RBE4, following treatment with the antiepileptic
drugs (AEDs), topiramate, phenobarbital, carbamazepine, tiagabine,
levetiracetam, and phenytoin, using Western blotting and immunocytochemistry
methods. Carbamazepine, phenobarbital and phenytoin induced
the highest levels of P-gp and MPRs expression that was associated
with increased activation of PXR and CAR receptors as compared
to levetiracetam, tiagabine and topiramate. We conclude that
P-gp and MRPs are differently overexpressed in GPNT and RBE4
by various AEDs and both PXR and CAR are involved in the drug-resistant
epilepsy induced by carbamazepine, phenobarbital and phenytoin.
Back to top]
A SELDI-TOF-MS Study in Lacunar Stroke with Subsequent
Haptoglobin Phenotyping
J. Staals, J.A.P. Bons, R.J. van Oostenbrugge,
I.L.H. Knottnerus, M.P. van Dieijen-Visser, F.G. Bouwman,
E.C. Mariman, J.R. Delanghe, J. Lodder and W.K.W.H.
Wodzig
Using Surface-Enhanced Laser Desorption / Ionization
Time-of-Flight Mass Spectrometry (SELDI-TOF-MS), we aimed
to detect differences in protein profile in serum samples
of two lacunar stroke subtypes.
SELDI-TOF-MS, followed by protein identification, was performed
in samples of 8 first-ever lacunar stroke patients with MR
imaging showing a single symptomatic lacunar lesion (type
1), and 8 with multiple additional “silent”
lacunar lesions and extensive white matter lesions (type
2). A 16 kDa protein, identified as alpha-2-chain of
haptoglobin (Hp), was found to be overrepresented in type
1 compared to type 2 (peak intensity 12.5 vs.
5.0; p=0.02). As a polymorphism with two alleles, Hp-1 and
Hp 2, determines the presence of alpha-1 and/or alpha-2-chains
in the Hp-molecule, Hp phenotypic analysis was performed.
Hp 1 : Hp-2 allele frequency was 0.562 : 0.438 in type
1 and 0.812 : 0.188 in type 2 (population reference
~0.4 : 0.6).
We conclude that the overrepresentation of the alpha-2-chain
in lacunar stroke type 1 compared to type 2 relates
to a higher Hp-2 allele frequency in the former. Yet, compared
to population reference, the phenotype distribution in both
patient groups deviates towards a high Hp-1 allele frequency.
Our findings suggest a role for the Hp gene in the etiology
of cerebral small vessel disease. Larger studies are now needed
to explore this new candidate gene.
Back to top]
Gastrin-Releasing Peptide Receptors Regulate Proliferation
of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase
Dependent Mechanism
D.G. Flores, C.B. de Farias, J. Leites, M.S.
de Oliveira, R.C. Lima, A.S.K. Tamajusuku, L.P. Di Leone,
L. Meurer, A.L. Brunetto,G. Schwartsmann, G. Lenz and
R. Roesler
Gastrin-releasing peptide (GRP) has been proposed as
a major growth factor in brain tumors, and GRP receptor (GRPR)
antagonists show antiproliferative effects in experimental
gliomas. However, the underlying molecular events downstream
of GRPR activation remain poorly understood. In the present
study, we examined the role of the GRPR in regulating proliferation
of glioma cells in vitro and its possible interaction
with the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
Expression of GRPR mRNA and protein in C6, U-87MG, and U-373MG
glioma cells was analyzed by reverse transcriptase polymerase
chain reaction (RT-PCR) and immunohistochemistry. Proliferation
of C6 and U-87MG, but not U-373MG cells was significantly
inhibited by the GRPR antagonist RC-3095, whereas the GRPR
agonist bombesin (BB) significantly enhanced proliferation
of C6 cells. The BB-induced stimulatory effect on cell proliferation
was prevented by either RC-3095 or the phosphatidylinositol
3-kinase (PI3K) inhibitor LY294002. Our results provide the
first evidence that the GRPR regulates proliferation of C6
glioma cells and suggest that PI3K is required for GRPR-mediated
stimulation of glioma growth.
Back to top]
Association of Soluble Adhesion Molecule and C-Reactive
Protein Levels with Silent Brain Infarction in Patients with
and Without Type 2 Diabetes
T. Umemura, T. Kawamura, T. Sakakibara, A. Kanai,
T. Sano, N. Hotta and G. Sobue
Silent brain infarction (SBI) is often detected on MR
imaging, however the pathogenesis is still unclear. We aimed
to investigate and compare the association of soluble adhesion
molecules and C-reactive protein levels with the prevalence
of SBI in patients with and without diabetes mellitus. We
recruited 130 patients (mean age 59.6 ± 7.6 yrs) with
type 2 diabetes and 130 age- and sex-matched non-diabetic
subjects. All subjects underwent head MRI to determine SBI.
We measured levels of soluble intercellular adhesion molecule
1(sICAM-1), vascular cell adhesion molecule 1(sVCAM-1), and
high sensitivity C-reactive protein (hs-CRP) and evaluated
intima-media complex thickness (IMT) in common carotid arteries
by ultrasound B-mode imaging. SBI was present in 36 ( 27.7%)
of the diabetic patients and 31 ( 23.8%) of the non-diabetic
subjects. Levels of sICAM-1, sVCAM-1 and IMT were all significantly
higher in diabetic patients than in non-diabetic subjects,
and were significantly increased in both subjects with SBI.
IMT was only positively correlated with sVCAM-1 levels in
diabetic and non-diabetic subjects. On the other hand, hs-CRP
levels were not significantly different in both subjects with
and without SBI. In addition, sICAM-1 levels were associated
with a significantly higher relative risk for the prevalence
of SBI in diabetic patients after multivariate adjustment.
Our study suggests that the associations between endothelial
dysfunction and presence of SBI may be stronger in diabetic
patients than in nondiabetic subjects. In particular, sICAM-1
may play an important role for the pathogenesis of SBI in
patients with diabetes mellitus.
Back to top]
Gelatin-Siloxane Hybrid Scaffolds with Vascular Endothelial
Growth Factor Induces Brain Tissue Regeneration
H. Zhang, T. Kamiya, T. Hayashi, K. Tsuru, K.
Deguchi, V. Lukic, A. Tsuchiya, T. Yamashita, S. Hayakawa,
Y. Ikeda, A. Osaka and K. Abe
In the brain after infarction or trauma, the tissue becomes
pannecrotic and forms a cavity. In such situation, a scaffold
is necessary to produce new tissue. In this study, we implanted
a new porous gelatin-siloxane hybrid derived from gelatin
and 3-(glycidoxypropyl) trimethoxysilane (gelatin-GPTMS) scaffolds
into a brain defect, and investigated whether it makes a new
brain tissue. In addition, vascular endothelial growth factor
(VEGF) was added on gelatin-GPTMS scaffolds and its effect
on tissue regeneration was examined. At 30 days after the
implantation, the marginal territory of the scaffolds became
occupied by newly formed tissue. Immunohistochemical analysis
revealed that the new tissue was constituted by endothelial,
astroglial and microglial cells, some of which were labeled
for bromodeoxyuridine (BrdU). Addition of VEGF promoted numbers
of these cells. Thus, combination of gelatin-GPTMS scaffolds
and VEGF is preferable for brain regeneration.
Back to top]
MIP-1α
and MCP-1 Induce Migration of Human Umbilical Cord
Blood Cells in Models of Stroke
L. Jiang, M. Newman, S. Saporta, N. Chen, C. Sanberg, P.R.
Sanberg and A.E. Willing
Monocyte chemoattractant protein-1 (MCP-1) and macrophage
inflammatory protein (MIP-1α)
are implicated in monocyte infiltration into the central nervous
system (CNS) under pathological conditions. We previously
showed that in vivo human umbilical cord blood cells
(HUCB) migrate toward brain injury after middle cerebral artery
occlusion (MCAO). We hypothesized that MCP-1 and MIP-1α
may participate in the recruitment of HUCB towards the injury.
Sprague-Dawley rats were subjected to middle cerebral artery
occlusion (MCAO), and 24 hours later the production of MCP-1
and MIP-1α
in the brain was examined with immunohistochemistry, ELISA,
and western blotting. The chemotactic effect of MCP-1 and
MIP-1α,
and the expression of MCP-1 receptor CCR2 and MIP-1α
receptor CCR1, CCR5 on the surface of HUCB were also examined.
MCP-1 and MIP-1α
expression were significantly increased in the ischemic hemisphere
of brain, and significantly promoted HUCB cell migration compared
to the contralateral side. This cell migration was neutralized
with polyclonal antibodies against MCP-1 or MIP-1α.
Also chemokine receptors were constitutively expressed on
the surface of HUCB cells. The data suggested that the increased
chemokines in the ischemic area can bind cell surface receptors
on HUCB, and induce cell infiltration of systemically delivered
HUCB cells into the CNS in vivo.
Back to top]
Erythropoietin and Oxidative Stress
K. Maiese, Z.Z. Chong, J. Hou and Y.C. Shang
Unmitigated oxidative stress can lead to diminished cellular
longevity, accelerated aging, and accumulated toxic effects
for an organism. Current investigations further suggest the
significant disadvantages that can occur with cellular oxidative
stress that can lead to clinical disability in a number of
disorders, such as myocardial infarction, dementia, stroke,
and diabetes. New therapeutic strategies are therefore sought
that can be directed toward ameliorating the toxic effects
of oxidative stress. Here we discuss the exciting potential
of the growth factor and cytokine erythropoietin for the treatment
of diseases such as cardiac ischemia, vascular injury, neurodegeneration,
and diabetes through the modulation of cellular oxidative
stress. Erythropoietin controls a variety of signal transduction
pathways during oxidative stress that can involve Janus-tyrosine
kinase 2, protein kinase B, signal transducer and activator
of transcription pathways, Wnt proteins, mammalian forkhead
transcription factors, caspases, and nuclear factor κB.
Yet, the biological effects of erythropoietin may not always
be beneficial and may be poor tolerated in a number of clinical
scenarios, necessitating further basic and clinical investigations
that emphasize the elucidation of the signal transduction
pathways controlled by erythropoietin to direct both successful
and safe clinical care.
Back to top]
HspB5/αB-Crystallin:
Properties and Current Progress in Neuropathy
Z. Hu and T. Li
HspB5/αB-crystallin
(αBC),
one of the most representative member of mammalian small heat
shock protein family (sHsp), shares the common features with
other nine members HspB1-B4 and HspB6-10. Meanwhile, it has
a strong antiapoptic effect; its interaction with cytoskeleton
participates in maintaining cell structure and plays an important
role in cytoprotection. Recent studies reveal that HspB5 has
a strong relationship with neurological diseases acting as
a protective molecular chaperone or in certain conditions,
a pathogenic factor. This review gives a brief introduction
on properties of HspB5, its current progress in neurological
diseases and potential therapeutic intervention in demyelinating
disease, neurodegenerative disease, myopathy and cerebrovascular
disease.
|
