| Current
Neurovascular Research
ISSN: 1567-2026
Current Neurovascular Research
Volume 6, Number 2, May 2009
Contents
ORIGINAL ARTICLES
Depressed Glucose Consumption at Reperfusion following Brain
Ischemia does not Correlate with Mitochondrial Dysfunction
and Development of Infarction: An in Vivo Positron
Emission Tomography Study Pp. 82-88
Abraham Martín, Santiago Rojas, Deborah
Pareto, Tomàs Santalucia, Olga Millán, Ibane
Abasolo, Vanessa Gómez, Jordi Llop, Joan D. Gispert,
Carles Falcon, Núria Bargalló and Anna
M. Planas
[Abstract] [Purchase
Article] [PMID:
19442156 PubMed - indexed for MEDLINE]
Bradykinin is Involved in the Mediation of Cardiac
Nociception during Ischemia through Upper Thoracic Spinal
Neurons Pp. 89-94
Chao Qin, Jian-qing Du, Jing-shi Tang and
Robert D. Foreman
[Abstract] [Purchase
Article] [PMID:
19442157 PubMed - indexed for MEDLINE]
Neutralization of Interleukin-1β
Reduces Vasospasm and Alters Cerebral Blood Vessel Density
Following Experimental Subarachnoid Hemorrhage in Rats Pp.
95-103
Halina Jedrzejowska-Szypulka, Magdalena Larysz-Brysz,
Michal Kukla, Miroslaw Snietura and Joanna Lewin-Kowalik
[Abstract] [Purchase
Article] [PMID:
19442158 PubMed - indexed for MEDLINE]
Presynaptic NR2B-Containing NMDA Autoreceptors Mediate
Gluta-matergic Synaptic Transmission in the Rat Visual Cortex
Pp. 104-109
Yan-Hai Li, Jue Wang and Guangjun Zhang
[Abstract] [Purchase
Article] [PMID:
19442159 PubMed - indexed for MEDLINE]
Perinatal Asphyxia in Preterm Neonates Leads to Serum
Changes in Protein S-100 and Neuron Specific Enolase
Pp. 110-116
Distefano Giuseppe, Curreri Sergio, Betta Pasqua,
Li volti Giovanni, Cilauro Salvatore, Alessandro Frigiola,
Huppi Petra and Amato Maurizio
[Abstract] [Purchase
Article] [PMID:
19442160 PubMed - indexed for MEDLINE]
Angelica Injection Improves Functional Recovery and
Motoneuron Maintenance with Increased Expression of Brain
Derived Neurotrophic Factor and Nerve Growth Factor Pp.
117-123
Qin Cui, Junjian Zhang, Lei Zhang, Ruiling Li
and Hui Liu
[Abstract] [Purchase
Article] [PMID:
19442161 PubMed - indexed for MEDLINE]
Neutralizing Endogenous VEGF Following Traumatic Spinal
Cord Injury Modulates Microvascular Plasticity but not Tissue
Sparing or Functional Recovery Pp. 124-131
Richard L. Benton, Melissa A. Maddie, Mark J.
Gruenthal, Theo Hagg and Scott R. Whittemore
[Abstract] [Purchase
Article] [PMID:
19442162 PubMed - indexed for MEDLINE]
REVIEW ARTICLE
Blood Brain Barrier Compromise with Endothelial Inflammation
may Lead to Autoimmune Loss of Myelin during Multiple Sclerosis
Pp. 132-139
Marian Simka
[Abstract] [Purchase
Article]
[PMID: 19442163 PubMed - indexed for MEDLINE]
Abstracts
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[Purchase
Article] [PMID:
19442156 PubMed - indexed for MEDLINE]
Depressed Glucose Consumption at Reperfusion following Brain
Ischemia does not Correlate with Mitochondrial Dysfunction
and Development of Infarction: An in Vivo Positron
Emission Tomography Study
Abraham Martín, Santiago Rojas, Deborah
Pareto, Tomàs Santalucia, Olga Millán, Ibane
Abasolo, Vanessa Gómez, Jordi Llop, Joan D. Gispert,
Carles Falcon, Núria Bargalló and
Anna M. Planas
Glucose consumption is severely depressed in the ischemic
core, whereas it is maintained or even increased in penumbral
regions during ischemia. Conversely, glucose utilization is
severely reduced early after reperfusion in spite that glucose
and oxygen are available. Experimental studies suggest that
glucose hypometabolism might be an early predictor of brain
infarction. However, the relationship between early glucose
hypometabolism with later development of infarction remains
to be further studied in the same subjects. Here, glucose
consumption was assessed in vivo by positron emission
tomography (PET) with 18F-fluorodeoxyglucose
(18F-FDG) in a rat model
of ischemia/reperfusion. Perfusion was evaluated by PET with
13NH3
during and after 2-hour (h) middle cerebral artery occlusion,
and 18F-FDG was given after
2h of reperfusion. Brain infarction was evaluated at 24h.
Mitochondrial oxygen consumption was examined ex vivo
using a biochemical method. Cortical 18F-FDG
uptake was reduced by 45% and 25% in the ischemic core and
periphery, respectively. However, substantial alteration of
mitochondrial respiration was not apparent until 24h, suggesting
that mitochondria retained the ability to consume oxygen early
after reperfusion. These results show reduced glucose use
at early reperfusion in regions that will later develop infarction
and, to a lesser extent, in adjacent regions. Depressed glucose
metabolism in the ischemic core might be attributable to reduced
metabolic requirement due to irreversible cellular injury.
However, reduced glucose metabolism in peripheral regions
suggests either an impairment of glycolysis or reduced glucose
demand. Thus, our study supports that glycolytic depression
early after reperfusion is not always related to subsequent
development of infarction.
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[Purchase Article] [PMID:
19442157 PubMed - indexed for MEDLINE]
Bradykinin is Involved in the Mediation of Cardiac Nociception
during Ischemia through Upper Thoracic Spinal Neurons
Chao Qin, Jian-qing Du, Jing-shi Tang and
Robert D. Foreman
Bradykinin is one of metabolites produced during myocardial
ischemia and infarction that can activate cardiac spinal (sympathetic)
sensory neurons to cause chest pain. The aim of this study
was 1) to characterize the responses of thoracic superficial
and deeper spinal neurons in rats to intrapericardial administration
of bradykinin as a noxious cardiac stimulus; 2) to compare
neuronal responses to bradykinin alone and a mixture of algogenic
chemicals (serotonin, prostaglandin E2,
histamine, adenosine and bradykinin) used in a previous study.
Extracellular potentials of single neurons in the T3
spinal cord were recorded in pentobarbital anesthetized, paralyzed,
and ventilated male rats. A catheter was placed in the pericardial
sac to administer 0.2 ml solution of bradykinin (10-5
M, 1 min). The results showed that 10/33 (30%) superficial
and 80/165 (48%) deeper spinal neurons responded to intrapericardial
bradykinin. All 10 superficial responsive neurons and 72/80
(90%) deeper neurons were excited; 7 (9%) neurons were inhibited;
one neuron showed excitation-inhibition response pattern.
Of 72 neurons excited by bradykinin, 35 and 47 neurons exhibited
short- and long-lasting responses patterns, respectively.
The proportions of response patterns and maximal excitatory
responses to bradykinin were similar to effects obtained with
a mixture of algogenic chemicals. However, the time to peak
(28.3±3.1
s) and recovery time of long-lasting excitatory responses
to bradykinin alone (125.2±8.9
s, n=47) were significantly shorter than the responses of
neurons to the algogenic mixture (38.6?3.8 s and 187.5±18.5
s, n=49, P<0.05).
In conclusion, bradykinin might play a key role in spinal
processing for cardiac nociception, although other components
released during ischemia might affect time characteristics
of a subtype of thoracic spinal neurons receiving noxious
cardiac input.
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[Purchase Article] [PMID:
19442158 PubMed - indexed for MEDLINE]
Neutralization of Interleukin-1β
Reduces Vasospasm and Alters Cerebral Blood Vessel Density
Following Experimental Subarachnoid Hemorrhage in Rats
Halina Jedrzejowska-Szypulka, Magdalena Larysz-Brysz,
Michal Kukla, Miroslaw Snietura and Joanna
Lewin-Kowalik
Subarachnoid hemorrhage (SAH) develops when extravasated
arterial blood enters subarachnoid space and mixes with cerebrospinal
fluid. As a result, many pathologies develop, including arterial
vasospasm that leads to the ischemia and hypoxia. Immuno-inflammatory
response is considered as the cause of numerous complications
following SAH.
In the study, we examined the role of one of major cytokines,
interleukin 1-beta (IL-1beta), on the vascular pathologies
after experimental SAH in adult rats. SAH was produced by
injection of 150 uL of autologous arterial blood into cisterna
magna. In 50% of animals, IL-1beta activity was inhibited
by intracerebroventricular administration of anti-rat IL-1beta
antibodies (SAH’ groups). Control group consisted of
sham-operated rats. Ninety minutes or 24 hrs following surgery,
animals were perfused transcardially and whole brains were
collected. Spasm index (ratio of vessel diameter to the mean
wall thickness) of basilar artery as well as blood vessel
density (number of vessels per square millimeter) at brain
stem and frontal part of the brain were measured. SAH led
to the vasospasm of basilar artery and increased the density
of blood vessel. Neutralization of IL-1beta activity significantly
reduced both the vasospasm and blood vessel density only 24
hrs after SAH. The results demonstrate an important role of
IL-1beta in the delayed development of vascular pathologies
after subarachnoid hemorrhage.
[Back to top] [Purchase
Article] [PMID:
19442159 PubMed - indexed for MEDLINE]
Presynaptic NR2B-Containing NMDA Autoreceptors Mediate Gluta-matergic
Synaptic Transmission in the Rat Visual Cortex
Yan-Hai Li, Jue Wang and Guangjun
Zhang
N-methyl-D-aspartate (NMDA) receptors (NMDA-Rs) have
different modulatory effects on excitatory synaptic transmission
depending on the receptor subtypes involved. The present study
investigated the subunit composition of the presynaptic NMDA-Rs
in layer II/III pyramidal neurons of the rat visual cortex.
We recorded evoked a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptor–mediated excitatory postsynaptic
currents (eEPSCs) using whole-cell voltage clamp with the
open-channel NMDA receptor (NMDA-R) blocker, (+)-5-Methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine
hydrogen maleate (MK-801), in the recording pipette. We found
that the paired-pulse ratio (PPR) by two successive stimuli
with inter-pulse intervals of 50 ms was significantly increased
by D-APV, a selective NMDA-R antagonist. Using a specific
antagonist for NR2B-NMDA-Rs, (αR,βS)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidinepropanol
hydrochloride (Ro 25-6981), instead of d-2-amino-5-phosphonovalerate
(D-APV), we found that the PPR of eEPSCs was also significantly
increased. Moreover, Zn2+,
an NR2A-NMDA-R antagonist, did not influence on the PPR. These
results suggest that presynaptic NR2B-containing NMDA-Rs are
located in layer II/III pyramidal neurons of the rat visual
cortex, and that presynaptic NR2B-containing NMDA autoreceptors
but not NR2A-containing NMDA autoreceptors mediate glutamate
release in the rat visual cortex. Moreover, these findings
may be clinically relevant to schizophrenia, where enhancing
NMDA-R function is considered to be a promising strategy for
treatment of the disease.
[Back to top] [Purchase
Article] [PMID:
19442160 PubMed - indexed for MEDLINE]
Perinatal Asphyxia in Preterm Neonates Leads to Serum Changes
in Protein S-100 and Neuron Specific Enolase
Distefano Giuseppe, Curreri Sergio, Betta Pasqua,
Li volti Giovanni, Cilauro Salvatore, Alessandro Frigiola,
Huppi Petra and Amato Maurizio
In preterm infants, neurological signs and clinical manifestations
of brain damage are limited criteria for diagnosis of neurologic
sequelae. Early indicators of brain damage are needed and
currently some specific biochemical markers of brain injury
are investigated to assess regional brain damage after perinatal
asphyxia in neonates. In this study Protein S-100 (PS-100)
and Neuron Specific Enolase (NSE) serum levels were studied
serially during the perinatal period in preterm neonates with
perinatal asphyxia as markers of glial and neuronal damage
respectively.
Thirty outborn preterm infants with perinatal asphyxia were
studied at 3, 24, 48 hours and 7 days of life. According to
Apgar scores at 1’ and cord blood pH and lacticidemia
(LA), patients were divided in two groups: 15 of them (GA
33±1.2 wk, BW 1790±383
g) with severe asphyxia (Apgar <4, pH7.0±0.08,
LA 6.29±0.79
mM/L) and 15 (GA 32±1.8
wk, BW 1810±290
g) with mild asphyxia (Apgar between 4-6, pH 7.18±0.05,
LA 2.59±0.61
mM/L). Ten gestational age matched healthy preterm neonates
were studied as control group. Cerebral ultrasound examinations
(7 MHz) were performed at birth and repeated at 3 weeks of
life. The results of this study show that neonates with severe
asphyxia at any time had significantly more elevated mean
serum levels of both markers compared to the group with mild
asphyxia and to the control group (p<0.05).
The values of control group were also significantly lower
in comparison with that of mild asphyxia. In neonates with
severe asphyxia, NSE values decreased constantly from birth
to the seventh day of life, while PS-100 showed a different
pattern increasing progressively between 3 h and 7 days. In
neonates with mild asphyxia serum values of both markers showed
decreasing levels through the study period.
The results of this study suggest that perinatal asphyxia
is associated with the release of different brain cellular
proteins in the blood of preterm infants with different time
course indicating specific regional cellular injury. The more
elevated levels of NSE at birth found in the newborns with
severe asphyxia could be considered as an early biomarker
of neuronal necrotic damage in the ischaemic phase of perinatal
cerebral hypoxic-ischaemic insult; progressive increase of
PS-100 during the first week of life in the same neonates
could be expression of apoptotic damage of glial cells occurring
in the reperfusion phase of cerebral ischaemia.
[Back to top] [Purchase
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19442161 PubMed - indexed for MEDLINE]
Angelica Injection Improves Functional Recovery and Motoneuron
Maintenance with Increased Expression of Brain Derived Neurotrophic
Factor and Nerve Growth Factor
Qin Cui, Junjian Zhang, Lei Zhang, Ruiling Li
and Hui Liu
This study assessed the neuroprotective effects of angelica
injection in the rat sciatic nerve crush injury (SCI). Forty
eight male Sprague Dawley rats were randomly divided into
4 groups: one was the sham group (S), which received sham
surgery and given saline injection and the others were received
SCI surgery and given saline injection, high and low dose
angelica injection for 4 weeks, respectively. The sciatic
functional index (SFI) in walking-track analysis, conductive
velocity (CV), the number of fluorogold labeled motoneurons,
and the expression patterns of brain derived neurotrophic
factor (BDNF) and nerve growth factor (NGF) in the sciatic
nerve and spine were examined. The results showed that SFI
descended gradually on day 7, and dropped more quickly on
day 28 in treatment groups (Low and High dose group). The
CV in treatment groups was higher than control group (C).
The numbers of motoneurons in treatment groups were larger
than C group (P<0.05),
but less than that in S group (P<0.01).
The expressions of BDNF and NGF protein in the groups received
SCI surgery were significantly lower than in S group, but
the protein expressions in the groups received angelica injections
were significantly higher than that in C group (P<0.01).
These findings suggested that angelica injection can improve
the sciatic nerve crush injury, and the mechanism might be
through the increase of BDNF and NGF protein expression.
[Back to top] [Purchase
Article] [PMID:
19442162 PubMed - indexed for MEDLINE]
Neutralizing Endogenous VEGF Following
Traumatic Spinal Cord Injury Modulates Microvascular Plasticity
but not Tissue Sparing or Functional Recovery
Richard L. Benton, Melissa A. Maddie, Mark J.
Gruenthal, Theo Hagg and Scott R. Whittemore
Acute loss of spinal cord vascularity followed by an
endogenous adaptive angiogenic response with concomitant microvascular
dysfunction is a hallmark of traumatic spinal cord injury
(SCI). Recently, the potent vasoactive factor vascular endothelial
growth factor (VEGF) has received much attention as a putative
therapeutic for the treatment of various neurodegenerative
disorders, including SCI. Exogenous VEGF exerts both protective
and destabilizing effects on microvascular elements and tissue
following SCI but the role of endogenous VEGF is unclear.
In the present study, we systemically applied a potent and
well characterized soluble VEGF antagonist to adult C57Bl/6
mice post-SCI to elucidate the relative contribution of VEGF
on the acute evolving microvascular response and its impact
on functional recovery. While the VEGF Trap did not alter
vascular density in the injury epicenter or penumbra, an overall
increase in the number of Griffonia simplicifolia
isolectin-B4 bound microvessels was observed, suggesting a
VEGF-dependency to more subtle aspects of endothelial plasticity
post-SCI. Neutralizing endogenous VEGF neither attenuated
nor exacerbated chronic histopathology or functional recovery.
These results support the idea that overall, endogenous VEGF
is not neuroprotective or detrimental following traumatic
SCI. Furthermore, they suggest that angiogenesis in traumatically
injured spinal tissue is regulated by multiple effectors and
is not limited by endogenous VEGF activation of affected spinal
microvessels.
[Back to top] [Purchase
Article] [PMID:
19442163 PubMed - indexed for MEDLINE]
Blood Brain Barrier Compromise with Endothelial Inflammation
may Lead to Autoimmune Loss of Myelin during Multiple Sclerosis
Marian Simka
Multiple sclerosis is an autoimmune disease characterized
by multifocal areas of inflammation and demyelination within
the central nervous system. The mechanism that triggers the
disease remains elusive. However, recent findings may indicate
that multiple sclerosis, at its source, could be a hemodynamic
disorder. It has been found that multiple sclerosis patients
exhibit significant stenoses in extracranial veins draining
the central nervous system (in azygous and internal jugular
veins), which are associated with significant pressure gradients
measured across strictures. Such anatomic venous abnormalities
were not found in the control group of healthy subjects. In
this review, it is hypothesized that pathological refluxing
venous flow in the cerebral and spinal veins increases the
expression of adhesion molecules, particularly intercellular
adhesion molecule-1 (ICAM-1), by the cerebrovascular endothelium.
This, in turn, could lead to the increased permeability of
the blood-brain barrier. Inflamed and activated endothelium
could secrete proinflammatory cytokines, including GM-CSF
and TGF-beta? In these settings, monocytes could transform
into antigen-presenting cells and initiate an autoimmune attack
against myelin-containing cells. Consequently, a potential
therapeutic option for multiple sclerosis could be pharmacotherapy
with either substances that strengthen the tight-junctions
barrier, or with agents that reduce the expression of adhesion
molecules. In addition, surgical correction could be an option
in some anatomical variants of pathologic venous outflow.
We are optimistic that a hemodynamic approach to the multiple
sclerosis pathogenesis can open a new chapter of investigations
and treatment of this debilitating neurologic disease.
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