Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

Background: Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion.

Effects of protein kinase C activators on Na, K-ATPase activity in rat brain microvessels.

In order to study the possible role of C kinase (PKC) on sodium pump of cerebral vessels, we used diacylglycerol (diC8: sn-1,2-dioctanoylglycerol) and phorbol esters (PMA: phorbol 12-myristate 13-acetate; PDA: phorbol 12,13-diacetate; 4 alpha-P: 4-alpha phorbol) as PKC activators, and examined their effects on Na,K-ATPase activity in rat brain microvessels (MVs). Rats were divided into non-treated (control; n = 9), four-vessel occlusion (4VO; 30-30 minutes ischemia and recirculation, n = 5), and middle cerebral artery occlusion (MCAO, n = 3) groups. MVs were passed through nylon meshes and were obtained by ultracentrifuge at 58000 g.

Biphasic constriction of rabbit basilar artery following experimental subarachnoid hemorrhage: a morphometric study.

To assess the changes in arterial structure resulting from subarachnoid hemorrhage, morphometric analysis was performed on basilar arteries from rabbits that had received an experimental subarachnoid hemorrhage up to 6 days earlier. For morphometric determination, the cross-sectional area of the media, the area of the lumen, and the length of the internal elastic lamina were measured planimetrically. The morphometric diameter of the lumen, the media-to-radius ratio, and several other morphometric parameters were also calculated.

Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm.

We previously suggested that activation of the protein kinase C-mediated contractile system may participate in the occurrence of chronic cerebral vasospasm. In the present study, we compared segments of normal beagle basilar arteries in vitro with segments of arteries undergoing chronic vasospasm to determine the responsiveness to various agonists such as serotonin, prostaglandin F2 alpha, and phorbol 12,13-diacetate as well as to external Ca2+. We also compared the effects of W-7 (a calmodulin inhibitor), nicardipine (a calcium channel blocker), and H-7 (a protein kinase C inhibitor) on the spontaneous tonus of arterial segments stabilized at a resting tension of 3 g.

Possible role of protein kinase C-dependent smooth muscle contraction in the pathogenesis of chronic cerebral vasospasm.

In the present study, we investigate the possible role of protein kinase C (PKC)-dependent smooth muscle contraction in cerebral vasospasm following subarachnoid hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of chronic vasospasm was angiographically confirmed on day 7 in the basilar artery, which was exposed via the transclival approach. The artery was superfused with aerated Krebs-Henseleit solution containing various agents, and the subsequent changes in the basilar artery diameter were recorded by successive angiography.

Endothelin family in human plasma and cerebrospinal fluid.

To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable.

Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study.

To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system.

Blood-brain barrier disturbance following subarachnoid hemorrhage in rabbits.

We studied disruption of the blood-brain barrier after experimental subarachnoid hemorrhage induced by an injection of 4 ml autologous arterial blood into the cisterna magna of rabbits. The animals were killed at 40 minutes, 6 hours, 1 day, 2 days, 4 days, or 6 days after subarachnoid hemorrhage. We assessed the integrity of the barrier function of intraparenchymal vessels in the ventral brain stem and cerebral hemispheres morphologically with transmission electron microscopy, using horseradish peroxidase as a tracer.

Effects of ebselen (PZ51) on ischaemic brain oedema after focal ischaemia in cats.

Using a transorbital middle cerebral artery (MCA) occlusion model in cats, we evaluated the anti-oedema effects of a new anti-inflammatory agent, ebselen (PZ51), on ischaemic cortical oedema caused by prolonged ischaemia and recirculation. Local cerebral blood flow was measured by the hydrogen clearance method in the MCA territory and the corresponding cortical specific gravity was assessed by a microgravimetric technique. Ebselen had no significant effect on normal and ischaemic lCBF, while it significantly ameliorated post-ischaemic hypoperfusion following recirculation.

Atrial natriuretic peptide in human cerebrospinal fluid.

We measured immunoreactive atrial natriuretic peptide (ANP) levels in cerebrospinal fluid (CSF) collected from patients with various neurologic disorders requiring diagnostic lumbar puncture. ANP was present in all of the CSF samples from 45 patients (1.7 +/- 0.

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups.

Blood-arterial wall barrier disruption to various sized tracers following subarachnoid haemorrhage.

Disruption of the blood-arterial wall barrier in the major cerebral arteries occurs following subarachnoid haemorrhage (SAH) and may be related to the pathogenesis of cerebral vasospasm. Using FITC dextrans of various sizes, the present study was undertaken to determine if the barrier disruption shortly after SAH occurs equally to various sized tracers. Forty-two Sprague-Dawley rats were divided into 5 groups.

Effect of hypoxia on the contractile response to KCl, prostaglandin F2 alpha, and hemoglobin.

The purpose of this experiment was to evaluate the effect of hypoxia on the in vitro contractile responses of canine basilar artery to KCl, prostaglandin (PG) F2 alpha, and hemoglobin. Hypoxia was induced by changing the bubbling gas mixture in the chamber from 95% O2/5% CO2 to 95% N2/5% CO2. Hypoxia augmented the contractile response developed at 95% O2 to 25 mM and 50 mM KCl, 3 X 10(-7) M and 10(-5) M PGF2 alpha, and 10(-6) M hemoglobin.

Effect of subarachnoid hemorrhage on endothelium-dependent vasodilation.

The effect of subarachnoid hemorrhage (SAH) on endothelium-dependent vasodilation of the isolated rabbit basilar artery was examined using an isometric tension recording method. The SAH was induced by injecting 5 ml of fresh arterial blood into the cisterna magna. Sixty-two rabbits were separated into four groups according to the timing of sacrifice: control rabbits, and operated rabbits sacrificed on Days 2, 4, and 6 after SAH.

A novel concept on the pathogenetic mechanism underlying ischaemic brain oedema: relevance of free radicals and eicosanoids.

A survey on literature reports and our own experimental studies on the pathogenetic mechanisms underlying ischaemic brain oedema is given and a new concept proposed. In regional incomplete ischaemia the lipoxygenase activity is enhanced, presumably caused by an increase of free radicals and hydroperoxides, leading to an enhancement of endothelial Na+, K+-AtPase and increased sodium and water transport from blood to brain. The aggravation of brain oedema and post-ischaemic hypoperfusion following recirculation appears to be mainly due to an activation of the cyclo-oxygenase pathway with release of oxidants from PGG2, which causes non-specific but detrimental damage to the endothelial and parenchymal cells.

[The pathomechanism underlying ischemic brain edema: the role of Na+, K+-ATPase of the brain microvessels].

In the present study, the anti-edema effect of AVS [1,2-bis (nicotineamide)-propane] was evaluated using the cat MCA occlusion model with or without recirculation. In the prolonged ischemia (PI) group, cortical edema as assessed by the changes in specific gravity, developed in those cortical areas where the mean 1-CBF was less than 25-30 ml/100 g/min during MCA occlusion (4 hours). In the recirculation group (2 hours' ischemia followed by 2 hours' recirculation: RC group), the ischemic threshold for edema development was almost the same as in the PI group.

Amelioration of ischaemic cerebral oedema by a free radical scavenger, AVS: 1,2-bis(nicotinamido)-propane. An experimental study using a regional ischaemia model in cats.

The effect of a free radical scavenger, AVS: 1,2-bis(nicotinamido)-propane, on the blood flow, oedema, and energy metabolites in the cortical area rendered ischaemic by the occlusion of the middle and the internal cerebral arteries was studied using cats. The development of cortical oedema was assessed by the changes in the specific gravity as well as the water and electrolyte contents of the cortical samples obtained 4 h after the arterial occlusion. Compared to the control group receiving saline, the AVS group exhibited a significant amelioration of cortical oedema, whereas no effect of AVS on the cortical blood flow was observed.

Sonic detection of intracranial aneurysm and AVM.

This paper describes a method of detecting intracranial aneurysm and arteriovenous malformation (AVM) by analysing weak sounds produced by the blood circulation at the affected part. There is thought to be no turbulence in the normal cerebrovascular system, whereas abnormalities such as aneurysm and AVM sometimes cause turbulence in the blood flow. Thus, a small fraction of the flow energy might be converted into an acoustically detectable noise.