Induction of hypercontractility in human cerebral arteries by rewarming following hypothermia: a possible role for tyrosine kinase

1997 ◽  
Vol 87 (3) ◽  
pp. 431-435 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang ◽  
R. Clinton Webb
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Cerebral Vessels ◽  
Sodium Orthovanadate ◽  
Content Type ◽  
Autopsy Specimens ◽  
The Brain

✓ Induction of hypothermia is used routinely in neurosurgical and cardiovascular operations to protect the brain from ischemic insult. However, despite a plethora of experimental evidence supporting the use of hypothermia to protect the brain from ischemia, clinical experience using deliberate hypothermia in humans has not shown a convincing benefit. The authors tested the hypothesis that hypothermia and rewarming alter tone in human cerebral vessels and may interfere with cerebral perfusion in the setting of deliberate hypothermia. They examined human cerebral arteries during hypothermia (32°C and 17°C) and during rewarming to delineate the direct effects of cooling and rewarming on cerebrovascular tone. Artery segments obtained from autopsy material and from specimens excised at elective temporal lobectomies were tested in tissue baths using isometric tension measurements. Temperature-induced changes in vascular tone were measured and quantified with respect to contractile responses to serotonin (5-HT; 10−6 M). Cooling induced mild relaxation in cerebral vessels (−38 ± 12% 5-HT response in 50 vessels from autopsy specimens, −69 ± 10% 5-HT response in 51 vessels from lobectomy specimens). On rewarming, vessels contracted significantly beyond their baseline tone (108 ± 18% 5-HT response in 50 vessels from autopsy specimens, 42 ± 12% 5-HT response in 51 vessels from lobectomy specimens). Rewarming-induced hypercontractility was inhibited by the tyrosine kinase inhibitor genistein (−5 ± 7% vs. 70 ± 23% 5-HT response, genistein vs. control, 14 segments, p < 0.05) and enhanced by the tyrosine phosphatase inhibitor sodium orthovanadate (339 ± 54% vs. 104 ± 20% 5-HT response, sodium orthovanadate vs. control, five segments, p < 0.05), indicating a possible role for tyrosine kinase activation in the rewarming-induced contraction.

Role of tyrosine kinase in erythrocyte lysate—induced contraction in rabbit cerebral arteries

1998 ◽  
Vol 89 (2) ◽  
pp. 289-296 ◽  
Author(s):  
Chul-Jin Kim ◽  
Kee-Won Kim ◽  
Jin-Woo Park ◽  
Jung-Chung Lee ◽  
John H. Zhang
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Relaxant Effect ◽  
Content Type ◽  
Basilar Arteries ◽  
Fine Print

Object. This study was undertaken to explore whether erythrocyte lysate, a proposed cause of vasospasm, produces vasoconstriction by activation of tyrosine kinase in rabbit cerebral arteries. Methods. Isometric tension was used to monitor contractions in rabbit basilar arteries induced by erythrocyte lysate, 5-hydroxytryptamine (5-HT), or KCl in the absence or presence of tyrosine kinase inhibitors. Erythrocyte lysate, 5-HT, or KCl produced concentration-dependent contractions in rabbit basilar arteries. Preincubation with the tyrosine kinase inhibitors tyrphostin A23 and genistein (30 and 100 µM), but not diadzein, an inactive analog of genistein, attenuated significantly the contraction induced by erythrocyte lysate (p < 0.05). Tyrphostin A23, genistein, and diadzein (30 µM) failed to reduce the contraction caused by 5-HT. Genistein, but not tyrphostin A23 or diadzein (30 µM), attenuated significantly the contraction induced by KCl (p < 0.05). In another series, arterial rings were initially contracted with erythrocyte lysate, 5-HT, or KCl and the relaxant effect of genistein was then tested. Genistein relaxed rabbit basilar arteries that had been contracted by exposure to erythrocyte lysate, 5-HT, or KCl (30–100 µM; p < 0.05). Conclusions. These data indicate that tyrosine kinase may play a role in the regulation of cerebral arterial contraction and tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm.

scholarly journals Topology of Streptococcus pneumoniae CpsC, a Polysaccharide Copolymerase and Bacterial Protein Tyrosine Kinase Adaptor Protein

2014 ◽  
Vol 197 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Jonathan J. Whittall ◽  
Renato Morona ◽  
Alistair J. Standish
Keyword(s):  
Streptococcus Pneumoniae ◽  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Kinase Activity ◽  
Tyrosine Phosphatase ◽  
Adaptor Protein ◽  
Tyrosine Kinase Activity ◽  
Content Type ◽  
Protein Tyrosine ◽  
C Terminus

In Gram-positive bacteria, tyrosine kinases are split into two proteins, the cytoplasmic tyrosine kinase and a transmembrane adaptor protein. InStreptococcus pneumoniae, this transmembrane adaptor is CpsC, with the C terminus of CpsC critical for interaction and subsequent tyrosine kinase activity of CpsD. Topology predictions suggest that CpsC has two transmembrane domains, with the N and C termini present in the cytoplasm. In order to investigate CpsC topology, we used a chromosomal hemagglutinin (HA)-tagged Cps2C protein inS. pneumoniaestrain D39. Incubation of both protoplasts and membranes with carboxypeptidase B (CP-B) resulted in complete degradation of HA-Cps2C in all cases, indicating that the C terminus of Cps2C was likely extracytoplasmic and hence that the protein's topology was not as predicted. Similar results were seen with membranes fromS. pneumoniaestrain TIGR4, indicating that Cps4C also showed similar topology. A chromosomally encoded fusion of HA-Cps2C and Cps2D was not degraded by CP-B, suggesting that the fusion fixed the C terminus within the cytoplasm. However, capsule synthesis was unaltered by this fusion. Detection of the CpsC C terminus by flow cytometry indicated that it was extracytoplasmic in approximately 30% of cells. Interestingly, a mutant in the protein tyrosine phosphatase CpsB had a significantly greater proportion of positive cells, although this effect was independent of its phosphatase activity. Our data indicate that CpsC possesses a varied topology, with the C terminus flipping across the cytoplasmic membrane, where it interacts with CpsD in order to regulate tyrosine kinase activity.

Microsurgical anatomy of the posterior cerebral artery

1978 ◽  
Vol 48 (4) ◽  
pp. 534-559 ◽  
Author(s):  
Arnold A. Zeal ◽  
Albert L. Rhoton
Keyword(s):  
Choroid Plexus ◽  
Posterior Cerebral Artery ◽  
Third Ventricle ◽  
Cerebral Arteries ◽  
Temporal Artery ◽  
Microsurgical Anatomy ◽  
Content Type ◽  
Lateral Posterior ◽  
Calcarine Fissure ◽  
The Brain

✓ In order to define the microsurgical anatomy, 50 posterior cerebral arteries (PCA's) were examined using × 3 to × 40 magnification. The PC A was divided into four segments: Pt was the segment proximal to the posterior communicating artery (PCoA); P2 extended from the PCoA to the posterior margin of the midbrain and was subdivided into an equal anterior (P2A) and posterior (P2P) half; P3 began at the posterior midbrain, ran within the quadrigeminal cistern, and ended at the anterior limit of the calcarine fissure. The PCA had three types of branches: 1) cortical branches to the cerebrum; 2) central branches to the brain stem; and 3) ventricular branches to the choroid plexus. The largest branches reaching the lateral surface of the cerebrum were located immediately anterior to the preoccipital notch, and in most cases were branches of the posterior temporal artery. This area offers a greater than 75% chance of finding a vessel large enough to perform a microvascular anastomosis. The central branches were of two types: 1) direct perforating, and 2) circumferential. The direct perforating branches arising on P1 were the posterior thalamoperforating arteries. The “thalamogeniculate artery,” the vessel said to be occluded in the “thalamic syndrome,” was also of the direct perforating type, but it was a series of small arteries arising from P2A and P2P rather than being a single vessel. The circumferential arteries usually arose from P1 and encircled the midbrain providing branches as far posteriorly as the colliculi. The branches to the choroid plexus were the medial and lateral posterior choroidal arteries; the former usually arose from P2A and entered the roof of the third ventricle, and the latter arose as a series of arteries from P2P and passed over the pulvinar to enter the lateral ventricle.

Role for tyrosine kinases in carbachol-regulated Ca entry into colonic epithelial cells

1995 ◽  
Vol 268 (1) ◽  
pp. C154-C161 ◽  
Author(s):  
G. Bischof ◽  
B. Illek ◽  
W. W. Reenstra ◽  
T. E. Machen
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Divalent Cations ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Colonic Epithelial Cells

We studied a possible role of tyrosine kinases in the regulation of Ca entry into colonic epithelial cells HT-29/B6 using digital image processing of fura 2 fluorescence. Both carbachol and thapsigargin increased Ca entry to a similar extent and Ca influx was reduced by the tyrosine kinase inhibitor genistein (50 microM). Further experiments were performed in solutions containing 95 mM K to depolarize the membrane potential, and the effects of different inhibitors on influx of Ca, Mn, and Ba were compared. Genistein, but not the inactive analogue daidzein nor the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2- methylpiperazine, decreased entry of all three divalent cations by 47-59%. In high-K solutions, carbachol or thapsigargin both caused intracellular Ca to increase to a plateau of 223 +/- 19 nM. This plateau was reduced by the tyrosine kinase inhibitors genistein (to 95 +/- 8 nM), lavendustin A (to 155 +/- 17 nM), and methyl-2,5-dihydroxycinnamate (to 39 +/- 3 nM). Orthovanadate, a protein tyrosine phosphatase inhibitor, prevented the inhibitory effect of genistein. Ca pumping was unaffected by genistein. Carbachol increased tyrosine phosphorylation (immunoblots with anti-phosphotyrosine antibodies) of 110-, 75-, and 70-kDa proteins, and this phosphorylation was inhibited by genistein. We conclude that carbachol and thapsigargin increase Ca entry, and tyrosine phosphorylation of some key proteins may be important for regulating this pathway.

Altered reactivity of human cerebral arteries after subarachnoid hemorrhage

1995 ◽  
Vol 83 (3) ◽  
pp. 510-515 ◽  
Author(s):  
Hisashi Onoue ◽  
Nobuyoshi Kaito ◽  
Masahiko Akiyama ◽  
Masato Tomii ◽  
Shogo Tokudome ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Vasoactive Agents ◽  
Content Type ◽  
Vasoactive Substances ◽  
Middle Cerebral Arteries ◽  
Prostaglandin F ◽  
Human Cadavers ◽  
Endothelium Dependent Relaxation

✓ To investigate the effects of subarachnoid hemorrhage (SAH) on the responsiveness of human cerebral arteries to vasoactive substances, the authors measured the isometric tension generated in helical strips of basilar and middle cerebral arteries isolated from human cadavers Contractions caused by KCl, prostaglandin F2α, noradrenaline, and serotonin were reduced in arteries obtained from cadavers with aneurysmal SAH damage and compared to those obtained from cadavers with no indication of intracranial diseases. Endothelium-dependent relaxation elicited by substance P and bradykinin, and endothelium-independent relaxation induced by prostaglandin I2 and nitroglycerin were also markedly decreased in arteries affected by SAH. However, the reduction in relaxation response to prostaglandin I2 was significantly less than that to the other vasodilator agents. These results indicate that human cerebral artery functions are severely impaired after SAH and that poor responses to vasoactive agents may result primarily from dysfunction of smooth-muscle cells.

Neuronal damage in gerbils caused by intermittent forebrain ischemia

1999 ◽  
Vol 91 (5) ◽  
pp. 835-842 ◽  
Author(s):  
Takatoshi Sorimachi ◽  
Hiroshi Abe ◽  
Shigekazu Takeuchi ◽  
Ryuichi Tanaka
Keyword(s):  
Neuronal Damage ◽  
Cerebral Arteries ◽  
Ischemic Insult ◽  
Content Type ◽  
Ischemic Episode ◽  
Temporary Occlusion ◽  
Ischemic Depolarization ◽  
The Brain ◽  
Severe Ischemia ◽  
Fine Print

Object. The purpose of this study was to investigate the possibility of preventing cumulative neuronal damage after repetitive severe ischemia.Methods. The authors monitored ischemic depolarization in the gerbil hippocampus, which has recently been shown to be a good experimental model of the effects of brief ischemia on the brain, and evaluated neuronal damage in the CA1 subregion 7 days after the ischemic insult. In a single-ischemia paradigm, the results indicate that induction of ischemia-induced neuronal damage depended on the duration of ischemic depolarization. Neuronal damage can be detected in the CA1 subregion after a period of depolarization lasting 210 seconds. Using a double-ischemia paradigm in which the animals were subjected to two periods of ischemia, there was apparently no accumulation of neuronal damage from the first ischemic episode to the second, provided the duration of the first period of ischemic depolarization did not exceed 90 seconds. Neuronal damage accumulated when the duration of the first ischemia episode exceeded 90 seconds, regardless of the duration of the reperfusion interval between the two ischemic insults. Finally, when the ischemic insult was spread over four separate episodes, each lasting 90 seconds (with a reperfusion interval of 5 minutes), neuronal damage was not found when the total depolarization period was less than 420 seconds.Conclusions. The authors conclude that cumulative neuronal damage may be avoided by adopting an intermittent ischemia approach. The implications of these results for human surgery requiring temporary occlusion of the cerebral arteries are discussed.

Asymmetry of pressure autoregulation after traumatic brain injury

2003 ◽  
Vol 99 (6) ◽  
pp. 991-998 ◽  
Author(s):  
Eric A. Schmidt ◽  
Marek Czosnyka ◽  
Luzius A. Steiner ◽  
Marcella Balestreri ◽  
Piotr Smielewski ◽  
...  
Keyword(s):  
Head Injuries ◽  
Cerebral Arteries ◽  
Brain Lesion ◽  
Fatal Outcome ◽  
Midline Shift ◽  
Content Type ◽  
Arterial Blood ◽  
Left And Right ◽  
The Brain ◽  
Fine Print

Object. The aim of this study was to assess the asymmetry of autoregulation between the left and right sides of the brain by using bilateral transcranial Doppler ultrasonography in a cohort of patients with head injuries. Methods. Ninety-six patients with head injuries comprised the study population. All significant intracranial mass lesions were promptly removed. The patients were given medications to induce sedation and paralysis, and artificial ventilation. Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in an invasive manner. A strategy based on the patient's cerebral perfusion pressure (CPP = ABP − ICP) was applied: CPP was maintained at a level higher than 70 mm Hg and ICP at a level lower than 25 mm Hg. The left and right middle cerebral arteries were insonated daily, and bilateral flow velocities (FVs) were recorded. The correlation coefficient between the CPP and FV, termed Mx, was calculated and time-averaged over each recording period on both sides. An Mx close to 1 signified that slow fluctuations in CPP produced synchronized slow changes in FV, indicating a defective autoregulation. An Mx close to 0 indicated preserved autoregulation. Computerized tomography scans in all patients were reviewed; the side on which the major brain lesion was located was noted and the extent of the midline shift was determined. Outcome was measured 6 months after discharge. The left—right difference in the Mx between the hemispheres was significantly higher in patients who died than in those who survived (0.16 ± 0.04 compared with 0.08 ± 0.01; p = 0.04). The left—right difference in the Mx was correlated with a midline shift (r = −0.42; p = 0.03). Autoregulation was worse on the side of the brain where the lesion was located (p < 0.035). Conclusions. The left—right difference in autoregulation is significantly associated with a fatal outcome. Autoregulation in the brain is worse on the side ipsilateral to the lesion and on the side of expansion in cases in which there is a midline shift.

scholarly journals Impairment of Autoregulatory Vasodilation by NAD(P)H Oxidase—Dependent Superoxide Generation during Acute Stage of Subarachnoid Hemorrhage in Rat Pial Artery

2002 ◽  
Vol 22 (7) ◽  
pp. 869-877 ◽  
Author(s):  
Hwa Kyoung Shin ◽  
Jeong Hyun Lee ◽  
Ki Young Kim ◽  
Chi Dae Kim ◽  
Won Suk Lee ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Acute Stage ◽  
Cerebral Vessels ◽  
Toxin B ◽  
Pial Artery ◽  
Acute Hypotension ◽  
Clostridium Difficile Toxin ◽  
Clostridium Difficile Toxin B

This study assessed the mechanism(s) by which the autoregulatory vasodilation of rat pial artery in response to acute hypotension during the acute phase of subarachnoid hemorrhage (SAH) was markedly blunted. Increased superoxide production from the cerebral vessels in response to NAD(P)H at 24 hours after SAH + NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) was inhibited by intracisternal administration of a tyrosine kinase inhibitor genistein (10 μmol/L) and Rac inhibitor Clostridium difficile toxin B (1 ng/mL) and a flavoenzyme inhibitor diphenyleneiodonium (10 μmol/L). The expression of gp91phox was enhanced by SAH + L-NAME from 12 to 24 hours, which was inhibited by genistein and toxin B, but not the p22phox. Increased membrane translocation of Rac after SAH + L-NAME was attenuated by both genistein and toxin B, whereas increased tyrosine kinase activity was blocked by genistein, but not by toxin B. The blunted autoregulatory vasodilation to acute hypotension was effectively recovered by genistein and C. difficile toxin B as well as by diphenyleneiodonium. In conclusion, SAH during acute stage causes an increase in NAD(P)H oxidase—dependent superoxide formation in cerebral vessels, which is due to activation of tyrosine phosphorylation-dependent increased expression of gp91phox mRNA and translocation of Rac protein, thereby resulting in a significant reduction of autoregulatory vasodilation.

Real-time detection of vascular occlusion and reperfusion of the brain during surgery by using infrared imaging

2002 ◽  
Vol 96 (5) ◽  
pp. 918-923 ◽  
Author(s):  
Joseph C. Watson ◽  
Alexander M. Gorbach ◽  
Ryszard M. Pluta ◽  
Ramin Rak ◽  
John D. Heiss ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Resolution ◽  
Real Time ◽  
Infrared Imaging ◽  
Cerebral Arteries ◽  
Infrared Camera ◽  
Collateral Flow ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Application of sensitive infrared imaging is ideally suited to observe blood vessels and blood flow in exposed organs, including the brain. Temporary vascular occlusion is an important part of neurosurgery, but the capacity to monitor the effects of these occlusions in real time is limited. In surgical procedures that require vascular manipulation, such as those involving aneurysms, arteriovenous malformations (AVMs), or tumors, the ability to visualize blood flow in vessels and their distribution beds would be beneficial. The authors recount their experience in the use of a sensitive (0.02°C), high-resolution (up to 50 µm/pixel) infrared camera with a rapid shutter speed (up to 2 msec/frame) for localizing cortical function intraoperatively. They observed high-resolution images of cerebral arteries and veins. The authors hypothesized that infrared imaging of cerebral arteries, performed using a sensitive, high-resolution camera during surgery, would permit changes in arterial flow to be be seen immediately, thus providing real-time assessment of brain perfusion in the involved vascular territory. Methods. Cynomolgus monkeys underwent extensive craniectomies, exposing the frontal, parietal, and temporal lobes. Temporary occlusions of the internal carotid artery and middle cerebral artery branches (30 events) were performed serially and were visualized with the aid of an infrared camera. Arteries and veins of the monkey brain were clearly visualized due to cooling of the exposed brain, which contrasted with blood within the vessels that remained at core temperature. Blood flow changes in vessels were seen immediately (< 1 second) in real time during occlusion and reopening of the vessels, regardless of the duration of the occlusion. Areas of decreased cortical blood flow rapidly cooled (−0.3 to 1.3°C) and reheated in response to reperfusion. Rewarming occurred faster in arteries than in the cortex (for a 20-minute occlusion, the change in temperature per second was 2 × 10−2°C in the artery and 7 × 10−3°C in the brain). Collateral flow could be evaluated by intraoperative observations and data processing. Conclusions. Use of high-resolution, digital infrared imaging permits real-time visualization of arterial flow. It has the potential to provide the surgeon with a means to assess collateral flow during temporary vessel occlusion and to visualize directly the flow in parent arteries or persistent filling of an aneurysm after clipping. During surgery for AVMs, the technique may provide a new way to assess arterial inflow, venous outflow, results of embolization, collateral flow, steal, and normal perfusion pressure breakthrough.

Cerebrospinal fluid may nourish cerebral vessels through pathways in the adventitia that may be analogous to systemic vasa vasorum

1982 ◽  
Vol 56 (4) ◽  
pp. 475-481 ◽  
Author(s):  
Nicholas T. Zervas ◽  
Theodore M. Liszczak ◽  
Marc R. Mayberg ◽  
Peter McL. Black
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Vessels ◽  
Subarachnoid Space ◽  
Cerebral Arteries ◽  
Cerebral Vessels ◽  
Vasa Vasorum ◽  
Cerebral Blood Vessels ◽  
Content Type ◽  
Large Proteins ◽  
Fine Print

✓ Cerebral blood vessels are devoid of vasa vasorum. Therefore, the authors have studied the microarchitecture of the adventitia of large feline cerebral vessels and systemic vessels of the same size, in an effort to determine how the vessels are nourished. The cerebral vessels contain a rete vasorum in the adventitia that is permeable to large proteins and is in continuity with the subarachnoid space. This substructure may be analogous to the systemic vasa vasorum and may contribute to the nutrition of the cerebral arteries.

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