| Current
Neurovascular Research
ISSN: 1567-2026
OPEN ACCESS PLUS
Contents
Nitric Oxide Production during Cerebral Ischemia and Reperfusion
in eNOS- and nNOS-Knockout Mice, 2010, 7, 23-31
Yasuo Ito, Takeshi Ohkubo, Yoshio Asano, Kimihiko
Hattori, Tomokazu Shimazu, Masamizu Yamazato, Harumitsu Nagoya,
Yuji Kato and Nobuo Araki
[Abstract] [Full
text article]
Cortical and Putamen Age-Related Changes in the Microvessel
Density and Astrocyte Deficiency in Spontaneously Hypertensive
and Stroke-Prone Spontaneously Hypertensive Rats,
2009, 6, 279-287
Marie-Françoise Ritz, Felix Fluri, Stefan
T. Engelter, Nicole Schaeren-Wiemers and Philippe
A. Lyrer
[Abstract] [Full
text article]
Venous Collateral Circulation of the Extracranial Cerebrospinal
Outflow Routes, 2009, 6, 204-212
Paolo Zamboni, Giuseppe Consorti, Roberto Galeotti,
Sergio Gianesini, Erica Menegatti, Giovanna Tacconi and
Francesco Carinci
[Abstract] [Full
text article]
Doppler Haemodynamics of Cerebral Venous Return,
2008, 5, 260-265
Erica Menegatti and Paolo Zamboni
[Abstract] [Full
text article]
MIP-1α
and MCP-1 Induce Migration of Human Umbilical Cord
Blood Cells in Models of Stroke, 2008, 5, 118-124
L. Jiang, M. Newman, S. Saporta, N. Chen, C. Sanberg, P.R.
Sanberg and A.E. Willing
[Abstract] [Full
text article]
Increased Neuronal Injury in Transgenic Mice with
Neuronal Overexpression of Human Cyclooxygenase-2 is reversed
by Hypothermia and Rofecoxib Treatment, 2007, 4,
274-279
Z. Xiang, S. Thomas and G. Pasinetti
[Abstract] [Full
text article]
Intracranial Venous Haemodynamics in Multiple Sclerosis,
2007, 4, 252-258
P. Zamboni, E. Menegatti, I. Bartolomei, R. Galeotti,
A.M. Malagoni, G. Tacconi and F. Salvi
[Abstract] [Full
text article]
Central Nervous System Circuitry and Peripheral Neural
Sympathetic Activity Responsible for Essential Hypertension,
2006, 3, 307-325
F. Lechin and B. van der Dijs
[Abstract] [Full
Text Article]
Abstracts
[Back to top]
Nitric Oxide Production during Cerebral Ischemia and
Reperfusion in eNOS- and nNOS-Knockout Mice
Yasuo Ito, Takeshi Ohkubo, Yoshio Asano, Kimihiko
Hattori, Tomokazu Shimazu, Masamizu Yamazato, Harumitsu Nagoya,
Yuji Kato and Nobuo Araki
[Full
text article]
The purpose of this study was to clarify the kinetics of nitric
oxide (NO) induced by either endothelial NO synthase (eNOS)
or neuronal NO synthase (nNOS) after transient global forebrain
ischemia. We investigated NO production and ischemic changes
to hippocampal CA1 neurons in eNOS knockout (-/-) mice and
nNOS (-/-) mice during cerebral ischemia and reperfusion.
NO production was continuously monitored by in vivo
microdialysis. Global forebrain ischemia was produced by occlusion
of both common carotid arteries for 10 minutes. Levels of
nitrite (NO2 -) and nitrate
(NO3 -), as NO metabolites,
in dialysate were determined using the Griess reaction. Two
hours after the start of reperfusion, animals were perfused
with 4% paraformaldehyde. Hippocampal CA1 neurons were divided
into three phases (severely ischemic, moderately ischemic,
surviving), and the ratio of surviving neurons to degenerated
neurons was calculated as the survival rate. The relative
cerebral blood flow (rCBF) was significantly higher in nNOS
(-/-) mice than in control mice after reperfusion. Levels
of NO3 - were significantly
lower in eNOS (-/-) mice and nNOS (-/-) mice than in control
mice during ischemia and reperfusion. NO3
- levels were significantly lower in nNOS (-/-) mice than
in eNOS (-/-) mice after the start of reperfusion. Survival
rate tended to be higher in nNOS (-/-) mice than in control
mice, but not significantly. These in vivo data suggest
that NO production in the striatum after reperfusion is closely
related to activities of both nNOS and eNOS, and is mainly
related to nNOS following reperfusion.
Theme: Disorders of the nervous system.
Topic: Ischemia.
[Back to top]
Cortical and Putamen Age-Related Changes in the Microvessel
Density and Astrocyte Deficiency in Spontaneously Hypertensive
and Stroke-Prone Spontaneously Hypertensive Rats
Marie-Françoise Ritz, Felix Fluri, Stefan
T. Engelter, Nicole Schaeren-Wiemers and Philippe
A. Lyrer
[Full text article]
Cerebral small vessel disease (SVD) is a major contributor
to dementia in the elderly, and hypertension represents a
major cause for developing the disease. However, little is
known about its development and progression. Modifications
of large cerebral arteries due hypertension are thought to
participate to the development of small ischemic infarcts,
but the status of the small vessels before the establishment
of hypertension is not well defined. Using spontaneously hypertensive
rats (SHR) and stroke-prone SHR (SP-SHR) as a models for SVD,
we analysed the effect of hypertension on the microvasculature
in the cortex and putamen, and on its relationship with astrocytes
in animals aged 2 to 9 months. Compared with the normotensive
Wistar-Kyoto rats (WKY), the densities of the collagen type
IV-positive capillaries were significantly higher in both
brain areas of young SHR and SP-SHR. In contrast, the expression
of the astrocytic marker GFAP was significantly lower in these
animals, whereas astrogliosis was observed after 6 months
in their cortex only. To investigate if chronic hypoxia occurs
due to the lower number of astrocytes in young SHR and SPSHR,
we evaluated the levels of HIF-1α
in both brain regions. The accumulation of HIF-1α
was not observed at the youngest ages, but was apparent in
neurons of 9-month-old SHR and SP-SHR. Our results indicate
that the brains of young SHR and SP-SHR rats show evidence
of cellular imbalance between microvessels and astrocytes
at the neurovascular unit that may lead to their higher vulnerability
to hypoxic events at older ages.
[Back to top]
Venous Collateral Circulation of the Extracranial
Cerebrospinal Outflow Routes
Paolo Zamboni, Giuseppe Consorti, Roberto Galeotti,
Sergio Gianesini, Erica Menegatti, Giovanna Tacconi and
Francesco Carinci
[Full
text article]
A new nosologic vascular pattern that is defined by chronic
cerebrospinal venous insufficiency (CCSVI) has been strongly
associated with multiple sclerosis. The picture is characterized
by significant obstacles of the main extracranial cerebrospinal
veins, the jugular and the azygous system, and by the opening
of substitute circles. The significance of collateral circle
is still neglected. To the contrary, substitute circles are
alternative pathways or vicarious venous shunts, which permit
the drainage and prevent intracranial hypertension. In accordance
with the pattern of obstruction, even the intracranial and
the intrarachidian veins can also become substitute circles,
they permit redirection of the deviated flow, piping the blood
towards available venous segments outside the central nervous
system. We review the complex gross and radiological anatomy
of collateral circulation found activated by the means of
EchoColor-Doppler and selective venography in the event of
CCSVI, focusing particularly on the suboccipital cavernous
sinus (SCS), the condylar venous system, the pterygoid plexus,
the thyroid veins, and the emiazygous-lumbar venous anastomosis
with the left renal vein.
[Back to top]
Doppler Haemodynamics of Cerebral Venous Return
Erica Menegatti and Paolo Zamboni
[Full
text article]
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, cost-effective 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.
[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
[Full
text article]
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]
Increased Neuronal Injury in Transgenic Mice with Neuronal
Overexpression of Human Cyclooxygenase-2 is reversed by Hypothermia
and Rofecoxib Treatment
Z. Xiang, S. Thomas and G. Pasinetti
[Full
text article]
Cyclooxygenase-2 (COX-2) is up-regulated during
ischemia. However, the role of COX-2 in neuronal injury is
still unclear. In this study we tested whether neuronal overexpression
of human COX-2 in a transgenic mouse model potentiates neuronal
injury after global ischemic insult. Further, we tested whether
the neuronal injury could be ameliorated by intra-ischemic
mild hypothermia (33-34°C) alone or in combination with
diet treatment of rofecoxib, a COX-2 specific inhibitor. Global
ischemia with intra-ischemic normothermia (36-37°C) resulted
in significantly higher neuronal damage in the CA1 region
of hippocampus of transgenic mice than in wild type controls,
confirming a deleterious role of COX-2 in ischemic neuronal
damage. Hypothermia significantly reduced neuronal damage
in both transgenic mice and wild type controls to the same
extent, suggesting that the aggravating effect of COX-2 could
be largely eliminated by hypothermia. When hypothermia was
combined with rofecoxib treatment, neuronal damage was further
reduced in response to global ischemia. The results suggest
that COX-2 inhibition by prophylactic treatment with rofecoxib
coupled with hypothermia at the time of acute stroke insult
could be an effective therapeutic approach in early stages
of stroke treatment in high risk patients.
[Back to top]
Intracranial Venous Haemodynamics in Multiple Sclerosis
P. Zamboni, E. Menegatti, I. Bartolomei, R. Galeotti,
A.M. Malagoni, G. Tacconi and F. Salvi
[Full
text article]
In multiple sclerosis (MS) plaques are known to be venocentric;
in addition, MS lesions and peripheral venous disorders share
a number of key features. To date, however, despite the anatomical
relationship between MS lesions and the venous system, no
information on the intracranial venous haemodynamics of MS
is available. Eighty-nine consecutive MS patients (58 relapsing-remitting,
31 secondary progressive) matched with 60 controls underwent
transcranial color-coded duplex sonography (TCCS). We assessed,
in supine as well as in sitting positions, the direction of
flow at the activation of the thoracic pump in the deep middle
cerebral veins (dMCVs), and in the transverse sinus (TS).
In the dMCVs, we also measured peak systolic velocity (PSV),
peak diastolic velocity (PDV), as well as the resistance index
(RI). Reflux/bidirectional flow rate was significantly higher
in the MS population determining also significant differences
in PDV, characterized by negative values (16.2±1 cm/sec
in controls vs. –1.3 ±2.6 cm/sec in MS, respectively,
p<0.0001). Consequently, RI was dramatically increased
in the MS group, affecting impedance of cerebral venous drainage
(0.48±0.04 in controls vs. 1.1 ±0.08 in MS,
respectively p<0.0001). Therefore, the detection of reflux
directed toward the subcortical grey matter was significantly
associated to highest disability scores (p < 0.0001). Our
study of MS patients demonstrated significant haemodynamic
alterations detected in veins anatomically related to plaque
disposition. Our findings should contribute towards understanding
the role of altered venous flow and tissue drainage in the
MS inflammatory chain, as well as in the neurodegenerative
process.
[Back to top]
Central Nervous System Circuitry and Peripheral Neural
Sympathetic Activity Responsible for Essential Hypertension
F. Lechin and B. van der Dijs
[Full
Text Article]
Both clinical and experimental studies dealing with patients
affected by idiopathic or essential hypertension (EH) are
devoted to the great deal of physiological, pharmacological
and pathological as well as therapeutical issues of EH. However,
most articles devoted to EH do not refer to the central nervous
system mechanisms underlying this disease and the channels
which allow that these mechanisms are funneled to the peripheral
autonomic nervous system and trigger this cardiovascular disorder.
In the present review article we attempted to reach this target
devoted to the central nervous system circuitry involved in
the cardiovascular pathophysiology. We postulated that EH
depends on the predominance of the binomial A5 noradrenergic
(NA) nucleus + median raphe serotonergic (5-HT) nucleus over
the (A6)-NA + dorsal raphe-5HT nuclei. This hypothesis receives
additional support from our results obtained throughout the
neuropharmacological therapy of this type of neurophysiological
disorder. Our therapeutical strategy is addressed to enhance
the activity of the (A6)-NA + dorsal raphe-5HT binomial circuitry.
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