Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient forebrain ischaemia model.

BACKGROUND: The current study was conducted to compare the effects of post-treatment with oestrogen on histological and neurological outcomes after short (7-day) and long (28-day) recovery periods in rats subjected to transient forebrain ischaemia. METHODS: Male Sprague-Dawley rats were randomly assigned to one of five groups: vehicle (7-day recovery period), vehicle (28-day recovery period), oestrogen (17ß-estradiol 200 µg/kg, 7-day), oestrogen (17ß-estradiol 200 µg /kg, 28-day), or sham surgical (n = 8 in each group). After forebrain ischaemia was induced with bilateral carotid artery occlusion and haemorrhagic hypotension (mean arterial pressure = 40 mmHg) for 10 min, the brain was reperfused for 7 or 28 days. Either 17ß-estradiol or vehicle was injected intravenously during the initial 2 min of reperfusion. To evaluate histological damage, the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted at 7 or 28 days after transient forebrain ischaemia. RESULTS: At 7 days after ischaemia, the number of intact neurons in the hippocampal CA1 subfield was significantly greater in the oestrogen group [57.5 (46.5)/mm: median (interquartile range)] than in the vehicle group [10 (19.5) /mm; P = 0.014]. However, there was no difference between groups at 28 days after ischaemia [vehicle: 11 (20)/mm vs. oestrogen: 6 (11)/mm]. The neurological deficit scores in the oestrogen and vehicle groups were not different from the sham group at any point post-ischaemia. CONCLUSION: The current study indicates that post-ischaemic administration of oestrogen provided short-term but not long-term neuroprotective effects in transient forebrain ischaemia in rats.

Long-term and spatial memory effects of selective ß1-antagonists after transient focal ischaemia in rats.

BACKGROUND: Although various reports have shown that ß-antagonists provide neuroprotective effects after cerebral ischaemia, their effect on spatial memory after transient focal ischaemia is not known. We investigated the treatment of ß1-antagonists on neurological outcome spatial memory for 1 month after focal cerebral ischaemia in rats. METHODS: Male rats randomly received an i.v. infusion of saline 0.5 ml h(-1), esmolol 200 µg kg(-1) min(-1), or landiolol 50 µg kg(-1) min(-1). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. The infarct areas in the hippocampus and striatum were measured after the final retention trial and neurological examinations. RESULTS: Neurological deficit scores in the landiolol- and esmolol-treated rats were significantly lower than in the control rats at 1, 4, 7, and 11 days after ischaemia (P<0.05). Using the Morris water maze to assess spatial memory, we found that escape latency and swimming path length to the platform were significantly shorter in the landiolol-treated rats, compared with the saline-treated rats at 4 and 11 days after ischaemia (P<0.05). The mean (SD) infarct area was 19.1 (8.0)% in the striatum and 18.6 (10.0)% in the hippocampus of the landiolol-treated rats, and 16.8 (14.0)% and 16.8 (15.0)% in the striatum and hippocampus, respectively, of esmolol-treated rats. This was significantly less than in control rats [striatum 31.7 (14.0)% and hippocampus 29.8 (13.0)%, P<0.05]. CONCLUSIONS: The current study indicates that although esmolol and landiolol provided long-term neuroprotection in terms of histological outcome, they had no effect on neurological outcome and spatial memory retention.

Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats.

BACKGROUND: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone. METHODS: Thirty-eight male Sprague-Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 degrees C); group H (saline 1 ml/kg, 35.0 degrees C); group D (dexmedetomidine 100 microg/kg, 37.5 degrees C); and group DH (dexmedetomidine 100 microg/kg, 35.0 degrees C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia. RESULTS: Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05). CONCLUSION: The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone.

The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in rats.

BACKGROUND: We investigated whether coadministration of lidocaine and dexmedetomidine would reduce brain injury following transient forebrain ischemia in rats to a greater extent than either drug alone. METHODS: Adult male Sprague-Dawley rats were anesthetized with halothane to maintain normocapnia and normoxia. Rats received subcutaneous injection of saline 1 ml/kg, lidocaine 10 mg/kg, dexmedetomidine 3 microg/kg, or lidocaine 10 mg/kg plus dexmedetomidine 3 microg/kg. Thirty minutes after the drug injection, forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries, and was confirmed by isoelectric EEG. At the end of 10-min ischemia, rats were reperfused. The same dose of drugs was administered 3, 24, and 48 h after ischemia. Neurological examination was done at 1, 2, and 7 days after ischemia. Seven days after ischemia, the brain was stained with hematoxylin and eosin. We counted ischemic cells in the CA1 hippocampal region, striatum, and cerebral cortex. We also measured extracellular glutamate and norepinephrine concentration in hippocampal CA1 in the four groups. RESULTS: As compared with saline-treated rats, rats receiving dexmedetomidine plus lidocaine showed less than neurological deficit scores at 2 and 7 days after ischemia, and had less ischemic cells in the CA1 region. However, administration of dexmedetomidine plus lidocaine did not alter the area under the glutamate concentration curve and norepinephrine concentration during ischemia in the CA1 region, compared with saline-treated rats. CONCLUSIONS: Our results suggest coadministration of lidocaine and dexmedetomidine improves the neurological outcome without alteration of glutamate and norepinephrine concentrations during forebrain ischemia in rats.

Effect of mivazerol, a alpha-agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats.

BACKGROUND: We have previously reported that mivazerol, a alpha(2)-agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 microg/kg (M20), and 40 microg/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5+/-0.1 degrees C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40-50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography. RESULTS: Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period. CONCLUSIONS: Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain.

Neuroprotective effect of mivazerol, an alpha 2-agonist, after transient forebrain ischemia in rats.

BACKGROUND: We examined whether mivazerol, an alpha2-agonist, had neuroprotective effects after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of four groups (n=10 each): control (C, normal saline) and mivazerol 10 microg/kg (M10), 20 microg/kg (M20) and 40 microg/kg (M40) groups. Thirty minutes after drug administration, forebrain ischemia was induced with hemorrhagic hypotension and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. The neurologic outcome was evaluated 24 h, 48 h and 7 days after ischemia, followed by histologic evaluation. RESULTS: The survival rate during 7 days was significantly lower in group M40 than in groups M10 and M20 (P<0.05). The neurologic outcome was significantly better in groups M10 and M20 than in group M40 7 days after ischemia (P<0.05). The number of intact neurons in hippocampal CA1 was significantly greater in group M20 than in the other groups (P<0.05). Neuronal injury in the neocortex was significantly less in group M20 than in groups C and M40 (P<0.05). CONCLUSIONS: Our results suggest that mivazerol, up to 20 microg/kg, provides neuroprotective effects, whereas 40 microg/kg may exaggerate neuronal injury after transient forebrain ischemia in rats.

Synthesis of differentially substituted hexaethynylbenzenes based on tandem Sonogashira and Negishi cross-coupling reactions.

[reaction: see text] Synthesis of polyethynyl-substituted aromatic compounds was achieved efficiently by the use of the Negishi cross-coupling reaction, and this method, coupled with the Sonogashira reaction, was applied to the synthesis of differentially substituted hexaethynylbenzenes from chloroiodobenzenes.

Synthesis and association behavior of butadiyne-bridged

Butadiyne-bridged [4(4)](2,6)pyridinophane and [4(6)](2, 6)pyridinophane derivatives were synthesized, and their heteroassociations with the corresponding metacyclophanes and complexations with organic cations were investigated.

Synthesis and anion-selective complexation of cyclophane-based cyclic thioureas

Cyclic thiourea derivatives having three different types of cyclophane structure, ortho-meta, meta-meta, and meta-para, and a lariat-type thiourea, were synthesized, and their anion-binding ability was examined. The association constants for the complexation between the receptors and several anions in DMSO-d(6) were measured by the titration method using (1)H NMR spectroscopy. All receptors, except for the meta-para cyclophane, exhibit selective binding to the dihydrogenphosphate anion, which is stronger than that of the acyclic reference compound. The lariat-type receptor binds anions even more strongly than the cyclic receptors which do not possess the third binding site.

[Role of antigen-antibody reaction in pulmonary hypertensive reaction after antigen challenge].

Pulmonary arterial pressure, airway pressure, and lung weight increase were studied after antigen (human O-N type erythrocytes) challenge in isolated-perfused sensitized rabbit lungs. To investigate whether these hemodynamic changes are mainly caused by antigen-antibody reaction or by the other mechanisms, we measured changes of pulmonary arterial and airway pressures, and lung weight gain after antigen challenge in perfused nonsensitized rabbit lungs. Thirteen nonsensitized rabbits were divided into 2 groups; in N group (n = 5), antigen was given into Krebs Hanseleit perfusate; in Ab group (n = 8), antibody was given into reservoir 30 min prior to antigen challenge. Pulmonary arterial pressure in Ab group was higher than in N group after antigen challenge. Maximal increase in pulmonary arterial pressure after antigen challenge depended on agglutinin titer of antibody in perfusate (delta Ppa = 0.068 x [titer]-0.146, r2 = 0.929). However, there were no significant differences between the two groups in changes of airway pressure and lung weight gain after antigen challenge. Although agglutinin titer of perfusate in Ab group was higher than our previous study, pulmonary hypertensive reaction to antigen in Ab group was significantly lower. It is concluded that the other mechanism besides antigen-antibody reaction itself can be responsible for hemodynamic changes after antigen challenge.

Studies on Ca2+-stimulated adenosine triphosphatase in rat submandibular glands: its distribution and properties.

Intracellular distribution and some characteristics of a Ca2+-stimulated adenosine triphosphatase (ATPase) in rat submandibular glands were investigated. This enzyme was activated by calcium alone, and magnesium was not necessary for its activation. Mg2+-stimulated ATPase also was investigated in the same enzyme preparations.