(Stroke. 2001;32:1658.)
© 2001 American Heart Association, Inc.
Original Contributions |
Threshold Duration of Ischemia for Myogenic Tone in Middle Cerebral Arteries
Effect on Vascular Smooth Muscle Actin
From the Departments of Obstetrics/Gynecology, Pharmacology, and Neurology, University of Vermont, Burlington (M.J.C., E.S.H., A.B.C.), and Oregon Stroke Center, Oregon Health Sciences University, Portland (N.L.).
Correspondence to Marilyn J. Cipolla, PhD, Departments of Obstetrics/Gynecology, Pharmacology, and Neurology, University of Vermont College of Medicine, Given C256, Burlington, VT 05405. E-mail mcipolla{at}zoo.uvm.edu
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Abstract |
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Background and Purpose—We investigated the effect of different periods of ischemia on the myogenic tone of middle cerebral arteries (MCAs) and tested the hypothesis that ischemia disrupts the actin cytoskeleton in vascular smooth muscle.
Methods—The MCA occlusion model was used in male Wistar rats (n=27) to induce different periods of ischemia (15, 30, and 120 minutes) with 24 hours of reperfusion. Successful occlusion was determined by laser-Doppler flowmetry. MCAs were then studied in vitro with a specialized arteriograph system that allowed control of transmural pressure and measurement of lumen diameter. After equilibration for 1 hour at transmural pressure of 75 mm Hg, lumen diameter was measured, and the amount of spontaneous myogenic tone was determined. Arteries were then fixed with 10% formalin while still pressurized in the arteriograph bath and stained for filamentous (F-) actin with fluorescently labeled phalloidin, a specific probe for F-actin. The amount of F-actin was quantified by confocal microscopy.
Results—The amount of tone was similar between control and 15 minutes of ischemia (27.0±2.0% and 25.3±1.7%, respectively; P>0.05) but was significantly diminished after 30 and 120 minutes (11.7±2.0% and 8.5±2.0%, respectively; P<0.01 versus control). F-actin content also decreased at the longer ischemic periods and correlated significantly with vascular tone (P=0.04) such that the lesser the tone, the lesser was the F-actin content. Fluorescence intensity for control and 15, 30, and 120 minutes of ischemia was (x107) 3.21±0.25, 2.54±0.32 (P>0.05), 2.32±0.15 (P<0.01), and 2.22±0.16 (P<0.01), respectively.
Conclusions—These results demonstrate that ischemia disrupts the actin cytoskeleton in smooth muscle and diminishes vascular tone of MCAs in a threshold-dependent manner. This effect likely exacerbates brain tissue damage during stroke, including infarction and edema formation.
Key Words: actins • cerebral arteries • cytoskeleton • reperfusion injury • stroke, acute • stroke, ischemic • rats
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Introduction |
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The cerebral circulation operates in a state of partial constriction or tone that provides a state from which an artery can increase or decrease diameter and hence cerebral blood flow (CBF) on demand.1 While there are several influences that determine vessel caliber (eg, neuronal, endothelial, metabolic), basal tone is primarily determined by the myogenic behavior of the cerebral vascular smooth muscle (VSM) that constrict in response to elevated pressure and dilate in response to decreased pressure.2 The innate myogenic tone of the cerebral VSM is crucial for establishment of an appropriate cerebrovascular resistance (CVR), which serves to protect downstream arterioles and capillaries in the face of changing perfusion pressures.3
Significant tissue damage occurs when autoregulation of CBF is lost. For example, reperfusion following transient cerebral ischemia causes autoregulatory loss and hyperperfusion.4 Cerebral hyperemia exacerbates neuronal injury and promotes brain edema due to a diminished CVR that exposes the microcirculation to excessive perfusion pressure.5 6 Although this period of postischemic hyperemia is due to vasodilatation of the cerebral vasculature, the mechanisms by which ischemia and reperfusion cause loss of myogenic tone are not clear. Accumulation of lactate and vasoactive ions is thought to have a role; however, this cannot completely explain the prolonged vasodilatation, particularly since it is demonstrated in vitro when these metabolites are not present and persists in humans for 2 to 3 weeks after stroke.6 7
In the present study we hypothesized that ischemia causes disruption of filamentous (F-) actin in cerebral artery VSM from occluded middle cerebral arteries (MCAs) that promotes the vasodilatation underlying postischemic hyperemia8 since this abundant protein is part of the contractile machinery and has been shown to be affected during ischemia.9 The MCA occlusion (MCAO) model was used in rats to induce different durations of ischemia, all with a constant reperfusion period of 24 hours.10 While this model is most widely used to study neuronal injury during stroke (ie, infarct size), we utilized it as a way of exposing MCAs to different periods of ischemia (0, 15, 30, and 120 minutes) since the MCA is focally occluded. Arteries were then studied in vitro with a system that allowed measurement of lumen diameter, control of transmural pressure (TMP), and chemical fixation for determination of F-actin content. We found that the amount of intrinsic tone MCAs possessed decreased with increasing ischemic duration that correlated significantly with F-actin content. In addition, the threshold duration of ischemia for myogenic tone was between 15 and 30 minutes of ischemia. These results are similar to the threshold duration of ischemia for edema formation, suggesting that loss of myogenic tone may be an important contributor to postischemic reperfusion injury.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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MCAO Model
Different periods of ischemia were produced by filament occlusion of the right MCA in male Wistar rats (weight, 280 to 300 g) with a modification of the technique developed by Koizumi et al.10 All procedures were approved by the Institutional Animal Care and Use Committee. The animals were anesthetized via inhalation mask with halothane and oxygen. With the aid of a dissecting microscope, the right carotid bifurcation was exposed, and the external carotid artery was coagulated distal to the bifurcation. After temporary ligature of the common carotid artery, a 5-0 nylon monofilament coated with silicone was inserted through the external carotid artery stump and gently advanced to occlude the origin of the MCA (Figure 1
). Successful occlusion of the MCA was
confirmed by laser-Doppler flowmetry. After initial
anesthesia but before midline incision for placement of the
monofilament, a skin incision in the right temporoparietal area was
made. The temporalis muscle was retracted, and the microtip of the
laser-Doppler fiber-optic probe was glued to the skull with
cyanoacrylate adhesive (Krazy Glue). The probe was left in place, and
CBF was recorded during the experiment.
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At 24 hours, before anesthesia was readministered, the animals were scored for neurological deficit by a 28-point scoring system that we developed.11 Two observers, blind to group, scored the animals independently, and the scores were averaged. After neurological deficit was scored and the MCA was removed for isolated artery studies, the brain was embedded in 1.5% agarose and sectioned with a Stoelting tissue slicer into 3-mm slices. The slices were placed in a well plate containing 2% 2,3,5-triphenyltetrazolium chloride (TTC) solution and allowed to develop for 30 minutes. The tissue was then placed in 10% formalin and scanned directly in the dish, and the images were placed in Adobe Photoshop. The National Institutes of Health image analysis program was used to measure the area of ischemia and total hemisphere volume. ANOVA was used to assess differences in lesion volume.
Preparation of MCAs and Pressurized Arteriograph
System
After neurological deficit analysis, the
animals were reanesthetized, and the brain was quickly removed
and placed in oxygenated physiological
saline solution (PSS). MCAs from the occluded side of the brain were
quickly dissected and mounted on 2 glass microcannulas within the
arteriograph chamber that was filled with PSS. The proximal cannula of
the chamber was connected to an in-line pressure transducer and
servomechanism that continually measured and adjusted TMP. The servo
system consisted of a miniature peristaltic pump and controller that
permitted TMP to be either maintained at a constant pressure (static)
or increased at a variable rate. The distal cannula was closed off
so that there was no flow within the arteries. The entire chamber was
placed on an inverted microscope with an attached video camera and
monitor. An optical window on the bottom of the chamber allowed lumen
diameter to be measured by video dimensional analysis, as
described
previously.12
Confocal Microscopy and Determination of F-Actin
Content
Arterial segments were fixed and
cannulated while pressurized at 75 mm Hg. Once diameter
measurements were obtained, 1 mL of 37% formaldehyde was added to the
10 mL of PSS already present in the bath to obtain a final
concentration of 3.7% (formalin). Arteries were fixed for 15 to 20
minutes, after which they were carefully removed from the cannulas,
stained for F-actin with phalloidin, with standard staining techniques,
and viewed with a BioRad MRC 1000 confocal
scanning laser microscope. Rhodamine fluorescence was detected
with an excitation of 568 nm and emission of 605 nm. Arteries were
imaged with a x20 objective, and
z-lines
representing approximately 1.5 µm thick and 1.0 µm
apart in the z axis (into and
out of plane) were obtained from optical sections of the arteries. To
be consistent, each artery was focused so that the top of the
artery was just out of the plane of focus (no image was present),
and each artery was sectioned the same distance into the surrounding
VSM. Arteries with tone at 75 mm Hg were used to set the iris and
gain optimally with the aid of image analysis software. A
fluorescence intensity histogram was recorded with a set
area that was appropriate for the size of the arteries. The gain and
iris were set the same for all arteries, and the total intensity (gray
scale value times the number of pixels that have that value) for a set
number of pixels (determined by the set area) was compared. Differences
in intensity were determined by ANOVA and considered significant at
P<0.05.
Experimental Protocol
The MCAO procedure was used to induce
ischemia of the MCA for different time periods: 15 minutes
(n=6), 30 minutes (n=7), or 120 minutes (n=8). Arteries subjected to
ischemia and reperfusion were compared with a group of vessels
from sham-operated control animals (n=6) in which the animal underwent
anesthesia and a midline incision, but without any
impairment of CBF. After the MCAO procedure, arteries were dissected
and mounted in the arteriograph bath. Arteries were equilibrated for 1
hour at TMP of 75 mm Hg, during which time spontaneous myogenic
tone developed. Lumen diameter was recorded after initial mounting
and again after the 1-hour equilibration period. Formalin was then
added directly to the bath while the artery was still mounted in the
chamber. The arteries were fixed for 20 minutes, after which they were
rinsed with PSS, removed from the cannulas, and stored in PSS at 4°C.
All arteries were stained at a later date for
F-actin.
Data Calculations and Statistical
Analysis
Percent tone was calculated as a percent decrease in
diameter from the baseline diameter at 24°C (room temperature) before
heating to 37°C. We and
others13 have found this
method to produce relaxed diameters within ±1% of relaxed diameters
induced by pharmacological inhibition of smooth muscle contraction. No
agents were given to relax smooth muscle since they could interfere
with F-actin organization. Statistical significance between groups was
determined by 1-way ANOVA with a post hoc Bonferroni test and
considered significant at
P<0.05.
Drugs and Solutions
PSS was composed of the following (mmol/L): NaCl
119.0, NaCHO3 24.0, KCl 4.7,
KH2PO4 1.18,
MgSO4 · 7H2O 1.17,
CaCl2 1.6, EDTA 0.026, and glucose 5.5.
Phalloidin was obtained from Molecular Probes
and mixed fresh before staining. TTC was purchased from
Sigma and mixed fresh before each
experiment.
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Results |
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Figure 1
shows a rat brain in which a 5-0 nylon monofilament
coated with silicone was surgically placed into the internal carotid
artery (ICA), where it was advanced until it occluded the MCA. This
MCAO procedure produces infarction similar to clinical stroke and is
transient such that the suture can be removed to allow reperfusion.
Because we were interested in how different periods of ischemia
affected the myogenic tone of MCAs, we used the MCAO model to focally
occlude the MCA and then recorded the change in lumen diameter of
isolated and pressurized MCAs. The utility of this model is further
strengthened because stroke outcome measures can be assessed, including
infarct size and neurological deficit.
The
Table shows several measurements of stroke
outcome. CBF, measured by laser-Doppler flowmetry,
decreased 56% to 72% for the experimental groups during the
ischemic period. The reduction in CBF was accompanied by damage
to brain tissue, producing infarction that was significant at 30 and
120 minutes of ischemia. Similarly, focal neurological deficit
was found to increase with the longer periods of ischemia, as
demonstrated by the increase in focal score.
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Diameter and Myogenic Tone in Ischemic
MCAs
Figure 2A shows a diameter tracing of MCAs from each
group of animals. Ischemic MCAs developed considerably less
myogenic tone at 75 mm Hg than control arteries, a response that
worsened as ischemic duration increased. Within 10 to 15
minutes of increasing pressure to 75 mm Hg, MCAs from control
animals spontaneously constricted, decreasing lumen diameter 27±2%.
Similarly, arteries that were subjected to 15 minutes of
ischemia developed 25.3±1.7% tone
(P>0.05). However, arteries
that were ischemic for 30 or 120 minutes had significantly
diminished tone and spontaneously contracted only 11.7±2% and
8.5±2% (P<0.01 for both),
respectively
(Figure 2B and
Table).
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VSM Actin Content in Ischemic MCAs
Figure 3A shows confocal micrographs of
F-actin–stained arteries. The intensity of staining decreased as
ischemic period increased.
Figure 3B shows average intensities for each group of MCAs.
The amount of staining followed a pattern similar to that of myogenic
tone, significantly diminishing with increasing ischemic
duration. Control MCAs had the greatest staining (3.21±0.25), which
was similar after 15 minutes of ischemia (2.54±0.32). F-actin
staining significantly diminished after 30 and 120 minutes of
ischemia, decreasing to 2.32±0.15 and 2.22±0.16, respectively
(P<0.01 versus
control).
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Discussion |
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In the present study we demonstrated that spontaneous myogenic tone was diminished after longer periods of ischemia, with the threshold duration between 15 and 30 minutes. In addition, the ischemia-induced loss of tone was associated with actin cytoskeletal disruption of the VSM. The loss of tone during ischemia and reperfusion could significantly affect stroke outcome since myogenic tone underlies autoregulation of CBF and CVR.3 Diminished CVR and autoregulatory failure are known to promote blood-brain barrier disruption and edema formation as a result of increased pressure on the microcirculation.5 6 In addition, ischemia-induced damage to the MCA may in and of itself negatively affect stroke outcome. For example, the increased wall tension due to dilation and loss of tone could increase vascular permeability of the MCA itself. Therefore, understanding how vascular structure and function are affected by ischemia and reperfusion, including the threshold durations for viability, is important in understanding the pathological process of stroke and for providing better stroke treatment.
It is well known that the depth and duration of
ischemia affect the outcome of stroke, giving rise to the
threshold concept of cerebral
ischemia.14 Our
previous studies demonstrated that longer periods of ischemia
and reperfusion resulted in complete loss of myogenic tone in MCAs,
whereas short periods produced normal
tone.15 These results
suggested that there may be a threshold duration of ischemia
and reperfusion for viability of VSM and myogenic tone. Since viability
thresholds tend to be flow dependent, changes in CBF were continuously
measured transcranially with the use of a laser-Doppler
flowmeter with a miniature fiber-optic
probe.15 All animals that
underwent the MCAO procedure experienced between 56% and 72% decrease
in CBF on MCAO, rates below those required to maintain brain
function,13 producing both
infarction and neurological deficit
(Table).
The time dependence of ischemic injury of the brain is
demonstrated in the
Table,
with longer durations giving rise to larger infarction and worse
neurological deficit. While the size of infarct increased with
increasing ischemic duration, as measured by TTC staining,
these values were not statistically significant, likely because
histological lesions require some time before they
become visible.16 Focal
neurological deficit, however, determined with a 28-point scoring
system,11 progressively
worsened with increasing ischemic period as well, becoming
significantly different at 30 and 120 minutes of ischemia.
While it is not surprising that these outcome measures of stroke
worsened as ischemic duration lengthened, the results of the
present study provide evidence that there is a threshold duration
of ischemia for myogenic tone of MCAs that is between 15 and 30
minutes
(Figure 2).
VSM contraction and myogenic tone have been shown to be
dependent on an intact actin cytoskeleton. Disruption of the actin
cytoskeleton by pharmacological agents that cause
depolymerization of actin filaments or inhibit
polymerization of monomeric G-actin into F-actin inhibits VSM
contraction and causes vasodilation and loss of
tone.8 17
Ischemia disrupts actin filaments in several cell types, which
is considered a major contributor to ischemic
damage.9 18 Given
the dependence of myogenic tone on an intact actin cytoskeleton, it is
possible that ischemia could be disrupting VSM actin and
underlie the loss of tone in the MCAs. The effect of ischemia
on F-actin was studied by chemically fixing pressurized MCAs with
formalin subsequent to tone measurements. The arteries were then
stained for F-actin with phalloidin and viewed with scanning laser
confocal microscopy.19
Ischemia had a profound effect on the F-actin content of
cerebral artery VSM such that the intensity of F-actin–stained
arteries diminished with increasing ischemic duration
(Figure 3A). The loss of F-actin in MCAs followed a pattern
similar to that for the loss of myogenic tone, strongly indicating an
ischemia-induced effect on cytoskeletal organization in VSM
(Figure 3B) as a mechanism underlying this loss of myogenic
vasoconstriction. However, while these results demonstrate that longer
periods of ischemia are associated with both diminished tone
and loss of F-actin, we do not know whether the ischemia causes
loss of tone, which in turn causes loss of F-actin, or vice versa. This
is an important consideration; other studies have demonstrated that
actin filament disruption causes loss of
tone,8 17 whereas
there have been no studies to our knowledge that have shown that loss
of tone affects actin structure. However, the causality and sequence of
these events are not known, and further studies are needed to fully
understand the nature of ischemia-induced loss of tone and
F-actin.
This study demonstrated that, similar to other cell types,
the actin cytoskeleton of VSM is sensitive to ischemic damage,
causing a loss of F-actin. The actin cytoskeleton is a complex and
dynamic structure, suggesting that there may be several mechanisms of
ischemia-induced damage that could be acting alone or in
combination to affect its organization and myogenic tone
(Figure 4). For example, actin polymerization is ATP
dependent, and therefore ATP depletion during ischemia and its
repletion during reperfusion likely have a profound effect on this
process.20 There are many
actin-binding proteins that control the dynamics and extent of
polymerization, such as actin depolymerizing factor, which has been
shown to be activated in kidney epithelial cells during
ischemia and to cause actin filament
disruption.21 Additionally,
myogenic tone can be affected by factors released from the
endothelium.22
For example, nitric oxide and superoxide anions are produced in large
quantities from both the vascular endothelium and
neurons during ischemia and can directly interact with actin
and interfere with
polymerization.23 24
Alteration in cytoskeletal structure and dynamics appears to be a
common pathway for ischemia-induced damage in many cell types,
including VSM. The subsequent loss of myogenic tone in cerebral
arteries is a process that likely aggravates ischemic brain
damage.
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The ischemia-induced effect on the contractile activity of MCAs appears specific for the myogenic response and pressure-induced contraction. In our previous studies, MCAs that were ischemic for 2 hours and reperfused for 24 hours developed little or no tone and did not respond myogenically to pressure, but they contracted to serotonin with the same sensitivity and reactivity as nonischemic control arteries, strongly indicating that ischemia can specifically affect myogenic contraction.15 Myogenic contraction can also be specifically disrupted by the actin depolymerizing agent cytochalasin B, without interfering with agonist-induced constriction. Previous studies have demonstrated that isolated cerebral arteries with tone at 75 mm Hg dilate and lose tone when exposed to 0.3 µmol/L cytochalasin B but contract vigorously to the protein kinase C activator (-)indolactam-V, indicating that pressure-induced myogenic contraction is more dependent on an intact and dynamic actin cytoskeleton than other mechanisms of contraction (eg, agonist induced).8 Myogenic contraction involves the transduction of a mechanical stimulus (pressure) into a cellular response (contraction). The actin cytoskeleton is in a unique position to both sense and respond to pressure with contraction. In fact, reorganization of the actin cytoskeleton in response to pressure or stretch is an important mechanotransduction process for many cell types.25 26 The exact mechanism of pressure-induced contraction is still unknown; however, since both ischemia and actin filament depolymerization produce a loss of tone, and ischemia promotes actin filament disruption, it is likely that the ischemia-induced effect on myogenic tone is due to a specific disruption of the actin cytoskeleton of cerebral artery VSM.
The MCAO model used in these studies has been increasingly
used for the study of ischemic stroke. In fact, this model has
greatly improved our understanding of stroke and will likely continue
to do so. While most investigators use this model to study damage to
brain tissue, we have used it as a way of inducing different periods of
ischemia and reperfusion on brain arteries. While we have found
this method quite useful, there are certain considerations that should
be addressed. First, since we are introducing a filament into the ICA,
it is possible that this procedure induces mechanical damage (eg,
denudation) to the ICA that could affect the MCA on reperfusion. We
have minimized this effect by using a silicone-coated monofilament. The
coating makes the filament very slick and therefore likely does not
cause damage to the ICA. Second, it is possible that there is a
gradient of damage along the MCA distal to the ICA. To eliminate
variability due to this effect, we have gone to great lengths to be
consistent in using the same segment of MCA in our studies.
Lastly, it is possible that the MCA itself could be damaged in this
procedure. This is unlikely since the monofilament is not inserted into
the MCA but is advanced only until it occludes the bifurcation at the
ICA
(Figure 1). We are therefore confident that the loss of tone
and F-actin noted in the MCA at longer periods of ischemia is
due to ischemic damage and not to the use of a filament in this
model.
In conclusion, myogenic tone is considerable and widespread in cerebral arteries, contributing significantly to autoregulation of CBF and CVR.1 2 3 We have demonstrated that longer periods of ischemia are associated with both loss of myogenic tone and disruption of VSM F-actin, with the threshold duration between 15 and 30 minutes. While the causality of these events is not clear, loss of autoregulation and diminished CVR during postischemic reperfusion are known to promote significant brain damage, including edema.5 Understanding how ischemia and reperfusion affect the structure and function of the cerebral arteries seems critical to understanding the pathophysiological mechanisms of stroke. Future treatments that target cerebrovascular protection may be beneficial and could minimize secondary brain tissue damage during reperfusion.
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Acknowledgments |
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This study was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke grants R55 NS37854 (Dr Cipolla) and RO1 NS40071 (Dr Cipolla).
Received January 5, 2001; revision received March 9, 2001; accepted March 26, 2001.
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References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
- Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2:161–192.[Medline] [Order article via Infotrieve]
- Johansson B. Myogenic tone and reactivity: definitions based on muscle physiology. J Hypertens. 1989;7(suppl 4):S5–S8.
- Mellander S. Functional aspects of myogenic vascular control. J Hypertens. 1989;7(suppl 4):S21–S30.
- Gourley JK, Heistad DD. Characteristics of cerebral hyperemia in the cerebral circulation. Am J Physiol. 1984;246:H52–H58.
-
Olsen TS, Larsen B,
Skriver EB, Herning M, Enevoldsen E, Lassen NA. Focal cerebral
hyperemia in acute stroke: incidence, pathophysiology and
clinical significance. Stroke. 1981;12:598–607.
[Abstract/Free Full Text] - Macfarlane R, Moskowitz MA, Sakas DE, Tasemiroglu E, Wei EP, Kontos HA. The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes. J Neurosurg. 1991;75:845–855.[Medline] [Order article via Infotrieve]
- Olsen TS. Regional cerebral blood flow after occlusion of the middle cerebral artery. Acta Neurol Scand. 1986;73:321–337.[Medline] [Order article via Infotrieve]
-
Cipolla M, Osol G.
Vascular smooth muscle actin cytoskeleton in cerebral artery forced
dilatation. Stroke. 1998;29:1223–1228.
[Abstract/Free Full Text] -
Molitoris BA.
Putting the actin cytoskeleton into perspective: pathophysiology of
ischemic alterations. Am J
Physiol. 1997;272:F430–F433.
[Abstract/Free Full Text] - Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema, I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jnp J Stroke. 1986;8:1.
- Clark WM, Lessov NS, Dixon MP, Eckenstein F. Monofilament intraluminal middle cerebral occlusion in the mouse. Neurol Res. 1997;19:641–648.[Medline] [Order article via Infotrieve]
-
Osol G, Laher I,
Cipolla M. Protein kinase C modulates basal myogenic tone in resistance
arteries from the cerebral circulation.
Circ Res. 1991;68:359–367.
[Abstract/Free Full Text] -
Dessy C, Matsuda
N, Hulvershorn J, Sougnez CL, Sellke FW, Morgan KG. Evidence for the
involvement of the PKC-
isoform in myogenic contraction of the
coronary microcirculation. Am
J Physiol. 2000;279:H916–H923.
- Hossmann K-H. Thresholds of ischemic injury. In: Ginsberg MD, Bogousslavsky J, eds. Cerebrovascular Disease Pathophysiology, Diagnosis, and Management. Vol 1. Oxford, UK: Blackwell Science; 1998:chap 13.
-
Cipolla M, McCall
A, Lessov N, Porter J. Reperfusion decreases myogenic reactivity and
alters middle cerebral artery function after focal cerebral
ischemia in rats.
Stroke. 1994;28:176–180.
[Abstract/Free Full Text] - Liszczak TM, Hedley-Whyte ET, Adams JF, Han DH, Kolluri VS, Vacanti FX, Heros RC, Zervas NT. Limitations of tetrazolium salts in delineating infarcted brain. Acta Neuropathol (Berl). 1984;65:150–157.[Medline] [Order article via Infotrieve]
-
Tseng S, Kim R,
Kim T, Morgan KG, Hai CM. F-actin disruption attenuates agonist-induced
[Ca+2], myosin phosphorylation and force in smooth
muscle. Am J Physiol. 1997;272:C1960–C1967.
[Abstract/Free Full Text] -
Kuhne W,
Besselmann M, Noll T, Muhs A, Watnabe H, Piper HM. Disintegration of
cytoskeletal structure of actin filaments in energy-depleted
endothelial cells. Am
J Physiol. 1993;264:H1599–H1608.
[Abstract/Free Full Text] - Haugland RP, You W, Paragas VB, Wells S. Simultaneous visualization of G- and F-actin in endothelial cells. J Histochem Cytochem. 1994;42:345–350.[Abstract]
-
Carlier M-F.
Actin: protein structure and filament dynamics.
J Biol Chem. 1991;266:1–4.
[Free Full Text] - Schwartz N, Hosford M, Sandoval RM, Wagner MC, Atkinson SJ, Bamburg J, Molitoris BA. Ischemia activates actin depolymerizing factor: role in proximal tubule microvillar actin alterations. Am J Physiol. 1999;276:F544–F551.
-
Cipolla M, Porter
JM, Osol G. High glucose concentrations dilate cerebral arteries and
diminish myogenic tone through an endothelial
mechanism. Stroke. 1997;28:405–411.
[Abstract/Free Full Text] -
Wang N, Butler
JP, Ingber DE. Mechanotransduction across the cell surface and through
the cytoskeleton. Science. 1993;260:1124–1127.
[Abstract/Free Full Text] - Banes AJ, Tsuzaki M, Yamamoto J, Fischer T, Brigman B, Brown T, Miller L. Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol. 1995;73:349–365.[Medline] [Order article via Infotrieve]
- Clancy R, Lesczynska J, Amin A, Lecartovsky D, Abramson SB. Nitric oxide stimulates ADP ribosylation of actin with association with the inhibition of actin polymerization in human neutrophils. J Leukocyte Biol. 1995;58:196–202.[Abstract]
-
Beckman JS,
Koppenol WH. Nitric oxide, superoxide and peroxynitrite: the good, the
bad and the ugly. Am J
Physiol. 1996;271:C1424–C1437.
[Abstract/Free Full Text]
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