Cerebral arterial constriction after experimental subarachnoid hemorrhage is associated with blood components within the arterial wall

1983 ◽  
Vol 58 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Theodore M. Liszczak ◽  
Vassilios G. Varsos ◽  
Peter McL. Black ◽  
J. Philip Kistler ◽  
Nicholas T. Zervas
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Structural Changes ◽  
Arterial Wall ◽  
Autologous Blood ◽  
Electron Microscopic Examination ◽  
Electron Microscopic ◽  
Content Type ◽  
Arterial Lumen ◽  
Angiographic Vasospasm ◽  
Basilar Arteries

✓ Sequential cisternal blood injections in dogs reproduce some of the morphological and physiological features seen in man after subarachnoid hemorrhage-induced vasospasm. This study reports the morphological features observed in cerebral vessels in areas exposed to subarachnoid blood. Subarachnoid hemorrhage was produced in dogs by two cisternal injections of non-heparinized autologous blood 48 hours apart. Dogs were sacrificed 48 hours after the second injection. Angiographic narrowing of the basilar artery was routinely present 48 hours after the second injection, and there was a good correlation between angiographic vasospasm and a narrowed arterial lumen at postmortem examination. All basilar arteries showed structural changes with electron microscopic examination; these included endothelial cell vacuoles, early smooth-muscle cell necrosis, intimal changes, and adventitial erythrocytes, leukocytes, and mast cells. The finding that accompanied vessel constriction most uniformly was packing of the adventitial cerebrospinal fluid spaces with erythrocytes. Angiographically visible spasm was resistant to vasodilators. These data suggest that infiltration of blood elements into the arterial wall is an important concomitant feature of morphological and angiographic vasospasm.

scholarly journals Mechanism of Cerebral Vasospasm Following Subarachnoid Hemorrhage in Monkeys

1992 ◽  
Vol 19 (4) ◽  
pp. 419-427 ◽  
Author(s):  
R.L. Macdonald ◽  
B.K.A. Weir ◽  
M.G.A. Grace ◽  
M.H. Chen ◽  
T.P. Martin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Structural Changes ◽  
Arterial Wall ◽  
Smooth Muscle Contraction ◽  
Wall Area ◽  
Angiographic Vasospasm ◽  
Vascular Smooth Muscle Contraction ◽  
Scanning Electron

ABSTRACT:This paper reviews our recent studies on the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH) in monkeys. Middle cerebral artery (MCA) vasospasm was maximal at 7 days, resolving by 14 days, and absent at 28 days after SAH. Arterial fibrosis was not detected during vasospasm, although there was intimal hyperplasia with fibrosis 28 days after SAH. On scanning electron microscopy, smooth muscle cells from vasospastic arteries had corrugated cell membranes and appeared similar to cells contracted pharmacologically, suggesting that vasospastic smooth muscle is contracted. Morphometric analysis of arteries obtained 7 days after SAH showed no significant increases in arterial wall area of vasospastic arteries compared with normal MCAs. The results suggest vasospasm in monkeys is not due to hypertrophy, hyperplasia, or fibrosis in the arterial wall. Vasospasm may be mainly vascular smooth muscle contraction, which damages the arterial wall, leading to secondary structural changes in the arterial wall which occur after angiographic vasospasm.

Cerebral perivascular nerves in subarachnoid hemorrhage

1986 ◽  
Vol 65 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Hideaki Hara ◽  
Michael Nosko ◽  
Bryce Weir
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Autologous Blood ◽  
Nerve Fibers ◽  
Content Type ◽  
Arterial Blood ◽  
Mild Reduction ◽  
Perivascular Nerves ◽  
Basilar Arteries ◽  
Repeat Angiography

✓ The authors have studied the changes induced by subarachnoid hemorrhage (SAH) in the density and distribution of cerebral perivascular nerves in monkeys and rats. The SAH was induced in monkeys by placement of an autologous blood clot after opening the basal cisterns over the arteries of the circle of Willis on one side. In the rat study, SAH was induced by injection of autologous arterial blood into the cisterna magna. The nerves examined were adrenergic nerves, acetylcholinesterase (AChE)-containing nerves, vasoactive intestinal polypeptide (VIP)-like immunoreactive nerves, and substance P-like immunoreactive nerves. In the monkey study, all animals underwent baseline cerebral angiography, then had repeat angiography just before sacrifice on Day 2, 7, 28, or 70 after SAH. Two sham-operated monkeys underwent the surgical procedure without clot placement and were sacrificed on postoperative Day 7, after repeat angiography. Clot placement in monkeys reduced staining of all middle cerebral artery (MCA) perivascular nerves for between 2 and 28 days post-SAH. The number of stained nerve fibers of MCA's on the non-operated side was slightly reduced on Days 2 and 7 after SAH. Sham-operated monkeys showed a mild reduction of staining in all nerves, but only on the operated side. Cerebral vasospasm was observed on all angiograms taken on Days 2 and 7 following SAH. No vasospasm was found in normal or sham-operated monkeys. The disappearance of nerve staining without associated vasospasm was found on the operated side of the sham-operated monkeys and on the clot side of the animal sacrificed on Day 28 after SAH. Rats sacrificed on Days 2 and 7 post-SAH showed reduction in adrenergic and VIP-like immunoreactive staining around basilar arteries, while nerves containing AChE were not affected. Saline-injected rats exhibited no change in the appearance of perivascular innervation. These results suggest that SAH as well as surgical manipulation of the vessel wall caused a reduction of the studied substances in cerebral perivascular nerves. This reduction in immunoreactive staining of perivascular nerves did not correlate with the development of angiographic vasospasm after SAH.

The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate

1998 ◽  
Vol 89 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Hisashi Onoue ◽  
Zvonimir S. Katusic
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Adenylate Cyclase ◽  
Autologous Blood ◽  
Delayed Rectifier ◽  
Relaxation Response ◽  
Content Type ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation ◽  
Basilar Arteries ◽  
Fine Print

Object. This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation. Methods. The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3′,5′-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (1027 mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10−3 mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10−5 mol/L), an adenosine 5′—triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 × 10−7 mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH. Conclusions. These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.

Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits

2004 ◽  
Vol 101 (1) ◽  
pp. 88-92 ◽  
Author(s):  
Gustavo Pradilla ◽  
Paul P. Wang ◽  
Federico G. Legnani ◽  
Lynn Ogata ◽  
Gregory N. Dietsch ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Subarachnoid Hemorrhage ◽  
Autologous Blood ◽  
Rabbit Model ◽  
Control Group ◽  
Lymphocyte Function ◽  
Content Type ◽  
Basilar Arteries ◽  
Fine Print

Object. Adhesion of leukocytes and their migration into the periadventitial space may be critical in the pathophysiology of vasospasm following subarachnoid hemorrhage (SAH). The cell adhesion molecules involved in this process are lymphocyte function—associated antigen—1 (CD11a/CD18) and macrophage antigen—1 (CD11b/CD18), which are present on neutrophils/macrophages, and intercellular adhesion molecule—1 (CD54), which is present in endothelial cells. A humanized monoclonal antibody (mAb), Hu23F2G, targets CD11/CD18 and prevents leukocyte adhesion to endothelial cells. In this study, systemic administration of Hu23F2G prevented vasospasm in the rabbit model of SAH. Methods. Twenty-six New Zealand White rabbits were injected with autologous blood into the cisterna magna to induce SAH, after which they were randomized to receive injections of either Hu23F2G (10 animals) or a placebo at 30 minutes and 24 and 48 hours after SAH (six animals). Control animals underwent sham operations (four animals) or SAH alone (six animals). The animals were killed 72 hours after SAH, their bodies perfused and fixed, and their basilar arteries processed for morphometric analysis. Peripheral white blood cells (WBCs) were counted at 72 hours. The percentages of lumen patency were compared using the Student t-test. The presence of neutrophils and macrophages was confirmed by immunohistochemical analysis in which a rat anti—rabbit anti-CD18 mAb and cresyl violet were used. Treatment with Hu23F2G resulted in the significant prevention of vasospasm. Animals treated with Hu23F2G had 90 ± 7% lumen patency compared with 65 ± 7% in the placebo group (p = 0.025). The percentage of lumen patency in the SAH-only group was 59 ± 10%. The mean WBC count was 16,300 ± 2710/µl in the treatment group, compared with 7000 ± 386/µl in the control group (p = 0.02). Administration of Hu23F2G produced increased numbers of WBCs in 70% of the animals treated. Conclusions. This study supports the concept that leukocyte—endothelial cell interactions play an important role in the pathophysiology of chronic vasospasm after SAH. Systemic therapy with an anti-CD11/CD18 mAb prevents vasospasm after SAH by inhibiting adhesion of neutrophils and macrophages and their migration into the periadventitial space.

A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys

1984 ◽  
Vol 60 (6) ◽  
pp. 1176-1185 ◽  
Author(s):  
Francisco Espinosa ◽  
Bryce Weir ◽  
Theodor Shnitka ◽  
Thomas Overton ◽  
Donald Boisvert
Keyword(s):  
Blood Clot ◽  
Autologous Blood ◽  
Ultrastructural Changes ◽  
Wall Thickening ◽  
Fish Scale ◽  
Double Blind ◽  
Content Type ◽  
Arterial Perfusion ◽  
Basilar Arteries ◽  
Trial Drug

✓ Chronic cerebral vasospasm was induced in monkeys by placement of an autologous blood clot after the basal cisterns had been opened over the arteries of the circle of Willis on one side. The experimental protocol was detailed in Part 1 of this paper. Twenty of the 30 monkeys studied from both groups (one receiving placebo and the other nimodipine) underwent cerebral fixation (Day 14) at controlled pressure by intra-arterial perfusion. The arteries at the base of the brain were studied by light microscopy and scanning (SEM) and transmission electron microscopy (TEM). Cerebral angiography on Day 7 showed that vasospasm was significantly more common (p < 0.0001) and more severe (p < 0.01) on the clot side compared to the control or non-clot side. Vasospasm was less severe on Day 14, just before sacrifice. On SEM, 80% of the 20 middle cerebral artery (MCA) specimens that had been in spasm (Day 7) showed marked corrugation, and in some the endothelium had a fish-scale appearance. All of the 10 MCA's on the clot side examined by TEM that had been in spasm (Day 7) showed marked changes such as endothelial swelling, subendothelial proliferation, corrugation of the elastic lamina, and myonecrosis. With few exceptions, none of the basilar arteries or MCA's on the non-clot (control) side showed any abnormalities. The pathological findings of vessels in spasm were considered to be slightly less severe in the nimodipine group; however, the trial drug (1 mg/kg/8 hrs) did not prevent such abnormalities from occurring. The ultrastructural changes in the arterial walls of specimens from both placebo and nimodipine groups in vasospasm are described. Since dramatic changes are present in the vessel walls even after radiologically visible vasospasm has almost completely abated, we believe that vasospasm is due to long-lasting smooth-muscle constriction and not to vessel wall thickening caused by a cellular or subcellular infiltrate.

Progression of partial experimental injury to peripheral nerve

1975 ◽  
Vol 42 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Alan R. Hudson ◽  
David G. Kline
Keyword(s):  
Recovery Of Function ◽  
Electron Microscopic Examination ◽  
Ground Substance ◽  
Electron Microscopic ◽  
Early Recovery ◽  
Content Type ◽  
Proximal Stimulus ◽  
Late Recovery ◽  
Fine Print ◽  
Experimental Injury

✓ Biopsies from partially lacerated nerves were taken at the sites of proximal stimulus, laceration, and distal recording, and from stimuli and recording sites of control nerves. Electron microscopic examination of the partially lacerated major fasciculus revealed three zones of injury. The laceration zone showed neurotemetic changes, the adjacent or intermediate zone, partial degeneration, and the zone most peripheral to the laceration, changes in ground substance. Progression of the original injury is apparently due to ongoing changes in the intermediate and peripheral zones while much of the relative early recovery is due to reversal of changes in these zones. Regeneration through the laceration or neurotemetic zone is limited but does account for a small amount of late recovery of function.

THE EFFECTS OF A CARDIAC GLYCOSIDE ON SUBCELLULAR STRUCTURES WITHIN NERVE CELLS AND THEIR PROCESSES IN SYMPATHETIC GANGLIA AND SKELETAL MUSCLE

1962 ◽  
Vol 40 (2) ◽  
pp. 303-315 ◽  
Author(s):  
R. I. Birks
Keyword(s):  
Skeletal Muscle ◽  
Structural Changes ◽  
Motor Nerve ◽  
Electron Microscopic Examination ◽  
Sympathetic Ganglia ◽  
Chloride Ions ◽  
Nerve Cells ◽  
Ion Concentration ◽  
Electron Microscopic ◽  
Pronounced Increase

Nerve cells and their processes in cat sympathetic ganglia and frog skeletal muscle have shown on electron microscopic examination alterations in subcellular morphology as a result of treatment with digoxin. Non-nervous cells were unaffected by the drug. These changes included, in ganglia, swelling of the affected cells, shrinkage of mitochondria with pronounced increase in internal density, swelling of Nissl substance in nerve cell bodies, and loss of structural detail in nerve processes. At the myoneural junction the motor nerve endings were swollen, mitochondria were altered, and the synaptic vesicles were reduced in numbers, those that remained being swollen. These changes were accompanied by invagination of the axon surface by Schwann cell processes.Cell swelling, but not the subcellular changes, was prevented by substitution of sulphate for chloride ions in the extracellular space. When the extracellular sodium ion concentration was reduced to 20 meq/l. the cells were completely protected against digoxin. It is concluded that swelling is caused by net uptake of sodium and chloride as a result of the known inhibitory action of digoxin on sodium extrusion by nerve cells. The possibility that these structural changes in subcellular organelles may be caused by a raised concentration of intracellular sodium ions, such as might occur during activity of excitable cells, is discussed.

Antisense preproendothelin-oligoDNA therapy for vasospasm in a canine model of subarachnoid hemorrhage

1999 ◽  
Vol 90 (6) ◽  
pp. 1105-1114 ◽  
Author(s):  
Hiroki Ohkuma ◽  
Ian Parney ◽  
Joseph Megyesi ◽  
Aziz Ghahary ◽  
J. Max Findlay
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Dna Sequences ◽  
Combined Treatment ◽  
Canine Model ◽  
Clot Lysis ◽  
Therapeutic Effects ◽  
Causative Role ◽  
Content Type ◽  
Basilar Arteries ◽  
Fine Print

Object. The purpose of this study is twofold: 1) to test antisense genetic techniques used in the prevention of cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH), targeting the endothelin-1 (ET-1) gene; and 2) to determine if fibrinolysis of subarachnoid clot with recombinant tissue plasminogen activator (rtPA) could enhance the effect of antisense treatment.Methods. A total of 39 dogs were studied in this experiment. Placebo (six animals), rtPA (six animals), antisense preproET-1 oligodeoxynucleotide (ASOD; five animals), or rtPA plus ASOD (combined treatment; six animals) was injected into the cisterna magna 30 minutes after a second SAH was induced on the 2nd day of the experiment. The animals were observed until Day 7, when they underwent follow-up angiography and then were killed; their basilar arteries were removed for analysis. Control animals included in this study (two animals in each group) received placebo, rtPA, ASOD, or rtPA plus ASOD without induction of SAH, or rtPA with mismatched (nonsense) preproET-1 oligodeoxynucleotide following SAH. Six additional dogs were analyzed earlier following SAH.Dogs that received placebo developed severe vasospasm (51 ± 8% of baseline caliber). Administration of ASOD alone resulted in a mild reduction in vasospasm (64 ± 13% of baseline caliber) and rtPA alone resulted in a moderate reduction in vasospasm (81 ± 5% of baseline caliber); however, the combined therapy of rtPA plus ASOD almost completely prevented vasospasm (95 ± 6% of baseline caliber), which was significantly different from all other groups (p < 0.05). Morphological analysis of the basilar arteries yielded results similar to angiography with respect to vasospasm severity. The ASOD treatment combined with rtPA resulted in reduced ET-1 expression, as demonstrated by immunohistochemical staining of the arteries, and reduced preproET-1 levels on Day 4, as measured by reverse transcription—polymerase chain reaction. Nonsense DNA sequences had no effect on the vessels.Conclusions. Antisense preproET-1 oligodeoxynucleotide treatment, when combined with clot lysis caused by rtPA, reduced vasospasm in the canine model of SAH, and this effect appeared to be related to reduced ET-1 synthesis. The results of this experiment support a causative role for ET-1 early in the course of vasospasm development in dogs. The apparent additive therapeutic effects of antisense and fibrinolytic treatments could be due to clot lysis, which allows better delivery of oligodeoxynucleotides to arteries within the subarachnoid space.

Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit

1986 ◽  
Vol 64 (3) ◽  
pp. 466-473 ◽  
Author(s):  
Stephanie S. Erlich ◽  
J. Gordon McComb ◽  
Shigeyo Hyman ◽  
Martin H. Weiss
Keyword(s):  
Cerebrospinal Fluid ◽  
Connective Tissue ◽  
Electron Microscopic Examination ◽  
Olfactory Pathway ◽  
Electron Microscopic ◽  
En Bloc ◽  
Major Pathway ◽  
Content Type ◽  
Csf Drainage ◽  
Fine Print

✓ Previous physiological studies indicate that the olfactory region serves as a major pathway for cerebrospinal fluid (CSF) drainage into the lymphatic system. The present study was undertaken to determine the ultrastructural characteristics of this egress route. New Zealand White rabbits received a single bolus injection of the tracer ferritin (MW 400,000) into both lateral ventricles in such a manner as not to raise the intraventricular pressure above the normal level. The animals were sacrificed via intracardiac perfusion of fixative between less than 12 minutes and 4 hours following injection. The cribriform region was removed en bloc, decalcified, sectioned coronally, and prepared for light and electron microscopic examination. The arachnoid, dura, and periosteum surrounding the fila olfactoria passing through the cribriform plate merge together and form the perineurium, which consists of multiple layers of loosely overlapping cells with widely separated junctions and few vesicles. The perineurium surrounding the olfactory filaments at the superficial submucosal level is only one cell thick. The subarachnoid space freely communicates with the perineural space surrounding each filament. No morphological barrier between the perineural space and the loose submucosal connective tissue was identified. Whether or not the perineurium was multi- or singlelayered, ferritin was noted in abundance between the loosely overlapping perineural cells and in the submucosal connective tissue. The distribution of ferritin at 12 minutes was similar to that at 4 hours; however, the quantity of ferritin was increased at 4 hours. These results indicate that no significant barrier to CSF drainage is present at the rabbit cribriform region and that CSF reaches the submucosal region rapidly via open pathways.

Effects of the Ca++-permeable nonselective cation channel blocker LOE 908 on subarachnoid hemorrhage—induced vasospasm in the basilar artery in rabbits

2003 ◽  
Vol 98 (3) ◽  
pp. 561-564 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Tomoh Masaki ◽  
Nobuo Hashimoto
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intravenous Administration ◽  
Basilar Artery ◽  
Channel Blocker ◽  
Autologous Blood ◽  
Content Type ◽  
Dependent Part ◽  
Before And After ◽  
Fine Print

Object. The Ca++ influx into vascular smooth-muscle cells (VSMCs) plays a fundamental role in the development and chronic effects of vasospasm after subarachnoid hemorrhage (SAH). The Ca++-permeable nonselective cation channels (NSCCs) are activated by several endothelium-derived constricting factors such as endothelin 1 (ET-1) and thromboxane A2. Moreover, the receptor-operated Ca++ channel blocker LOE 908 inhibits ET-1—induced extracellular Ca++ influx via NSCCs in the VSMCs of the basilar artery (BA) and the NSCC-dependent part of ET-1—induced vasoconstriction of BA rings. The purpose of the present study was to evaluate the in vivo role of LOE 908 on SAH-induced vasospasm. Methods. Forty-two Japanese white rabbits were assigned to seven groups. Treatment groups consisted of the following: 1) control rabbits without SAH that received a cisternal injection of saline; 2) rabbits with SAH that were subjected to the intravenous administration of saline; 3 through 6) rabbits with SAH that underwent the intravenous administration of 0.01, 0.1, 1, or 10 mg/kg LOE 908, respectively; and 7) rabbits without SAH that underwent the intravenous administration of 10 mg/kg LOE 908. Autologous blood was injected into the cisterna magna. The caliber of the BA was measured on angiographic studies before and after the cisternal injection of autologous blood. The intravenous injection of LOE 908 inhibited the magnitude of an SAH-induced vasosapsm. In addition, the concentration of LOE 908 required to relax vasospasm (1 mg/kg) correlated with that required to block Ca++ influx into VSMCs. Conclusions. The Ca++ channel blocker LOE 908 may inhibit the magnitude of an SAH-induced vasospasm by blocking the influx of Ca++ through NSCCs in rabbit BAs. Blocking the NSCCs may represent a new treatment for cerebral vasospasm after SAH.

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