Ischemic Edema Research Articles

Effect of Endovascular Hypothermia on Acute Ischemic Edema: Morphometric Analysis of the ICTuS Trial

Pilot studies of hypothermia for stroke suggest a potential benefit in humans. We sought to test whether hypothermia decreases post-ischemic edema using CT scans from a pilot trial of endovascular hypothermia for stroke. Eighteen patients with acute ischemic stroke underwent therapeutic hypothermia (target = 33 degrees C) for 12 or 24 h followed by a 12-h controlled re-warm using an endovascular system. CT scans obtained at baseline, 36-48 h (right after cooling and re-warming) and 30 days were digitized, intracranial compartment volumes measured using a validated stereological technique, and the calculated change in CSF volume between the three time-points were used as an estimate of edema formation in each patient. Patients were grouped retrospectively for analysis based on whether they cooled effectively (i.e., to a temperature nadir of less than 34.5 degrees C within 8 h) or not. Eleven patients were cooled partially or not at all, and seven were effectively cooled. Baseline demographics and compartment volumes and densities were similar in both groups. At 36-48 h, the total CSF volume had significantly decreased in the not-cooled group compared to the cooled group (P < 0.05), with no significant difference in mean volume of ischemia between them (73 +/- 73 ml vs. 54 +/- 59 ml, respectively), suggesting an ameliorative effect of hypothermia on acute edema formation. At 30 days, the difference in CSF volumes had resolved, and infarct volumes (73 +/- 71 ml vs. 84 +/- 102 ml, respectively) and functional outcomes were comparable. Endovascular hypothermia decreases acute post-ischemic cerebral edema. A larger trial is warranted to determine if it affects final infarct volume and outcome in stroke.

TWEAK and the Central Nervous System

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily that acts on responsive cells via binding to a cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK can regulate numerous cellular responses in vitro and in vivo. Recent studies have indicated that TWEAK and Fn14 are expressed in the central nervous system (CNS), and that in response to a variety of stimuli, including cerebral ischemia, there is an increase in TWEAK and Fn14 expression in perivascular astrocytes, microglia, endothelial cells, and neurons with subsequent increase in the permeability of the blood-brain barrier (BBB) and cell death. Furthermore, there is a growing body of evidence indicating that TWEAK induces the activation of the NF-kappaB in the CNS with release of proinflammatory cytokines and matrix metalloproteinases. In addition, inhibition of TWEAK activity by either treatment with a Fn14-Fc fusion protein or neutralizing anti-TWEAK antibodies has shown therapeutic efficacy in animal models of ischemic stroke, cerebral edema, and multiple sclerosis.

Experimental ischemic brain edema: morphological and magnetic resonance imaging findings

Magnetic resonance (MR) imaging is a powerful tool for detecting and characterizing ischemic edema, a serious complication of ischemic cerebrovascular disorders. In this article the authors investigate the relationships between MR imaging findings and structural/ultrastructural changes in ischemic brain edema by using various animal models of experimental cerebral ischemia. The authors observed the following: 1) Ischemic edema was detectable by diffusion weighted MR imaging as early as 15 minutes after the onset of vascular occlusion. A decrease in the apparent diffusion coefficient (ADC) corresponded to the early cellular/cytotoxic type of brain edema and the decrease was proportionate to the degree of intracellular water accumulation. 2) Postischemic transient normalization of the ADC after the initial decrease did not signify histological recovery but rather slowly progressing infarction. 3) Histological degradation of postischemic tissue correlated with the decrease in tissue elasticity and the magnetization transfer ratio. 4) Transient cytotoxic edema localized in the substantia nigra preceding neuronal death was detectable on MR images after ipsilateral striatal infarction. Thus, MR imaging is a powerful tool for detecting and characterizing brain edema associated with ischemic stroke.

Blood pressure lowering in acute ischaemic stroke: an update on the role of angiotensin receptor blockers

Blood pressure lowering in acute ischaemic stroke: an update on the role of angiotensin receptor blockers

Ischemic Brain Tissue Water Content: CT Monitoring during Middle Cerebral Artery Occlusion and Reperfusion in Rats1

To prospectively perform computed tomography (CT) in rats to determine whether ischemic edema can be reversed by using early arterial reperfusion. This study was approved by the local animal protection committee. A suture model was used to occlude the right middle cerebral artery (MCA) in rats for 1, 2, 3, or 4 hours. X-ray attenuation of the brain was measured directly before reperfusion and repeatedly during reperfusion for up to 24 hours. Infarct volumes were determined with triphenyltetrazolium chloride staining. Means of attenuation and infarct volume were compared between hemispheres and groups with a paired t test and analysis of variance. Mixed linear models were applied to compare attenuation among groups over time. During MCA occlusion, attenuation decreased to 69.3 HU +/- 1.9 (standard deviation) after 1 hour (n=12), 66.6 HU +/- 2.0 after 2 hours (n=10), 65.4 HU +/- 2.9 after 3 hours (n=11), and 64.1 HU +/- 1.8 after 4 hours (n=9) (P<.0001). After reperfusion, attenuation remained stable in the 1-hour occlusion group (P=.16) but further and steadily declined in the 2-, 3-, and 4-hour occlusion groups (P<.001). Attenuation during reperfusion in the 1-hour occlusion group differed significantly from that in the 2-, 3-, and 4-hour occlusion groups. CT is able to help monitor ischemic edema after MCA occlusion and reperfusion. Ischemic brain edema was not consistently reversible with reperfusion, even after 1 hour of occlusion, and further increased with reperfusion induced at 2 hours or later.

Cerebral edema and its treatment

Cerebral edema is a life-threatening condition that develops as a result of an inflammatory reaction. Most frequently, this is the consequence of cerebral trauma, massive cerebral infarction, hemorrhages, abscess, tumor, allergy, sepsis, hypoxia, and other toxic or metabolic factors. At present, the following types of cerebral edema are differentiated: the vasogenic cerebral edema resulting from an increased permeability of the endothelium of cerebral capillaries to albumin and other plasma proteins; the cytotoxic cerebral edema resulting from the exhaustion of the energy potential of cell membranes without damage to the barrier; the hydrostatic cerebral edema resulting from disturbance of the autoregulation of cerebral blood circulation; the osmotic cerebral edema resulting from dilution of blood; and the interstitial cerebral edema resulting from acute hydrocephaly. Some authors also differentiate ischemic cerebral edema. At present, when various traumas and traumatic cerebral injuries are frequent causes of death in young people, treatment strategy for cerebral edema is of utmost importance. Monitoring of the patient's condition in the intensive care unit is a necessity. It is important to ensure proper positioning of the patient--the head should be tilted at 30 degrees in order to optimize the cerebral perfusion pressure and control of the increase in intracranial pressure. Hyperventilation should be applied. Controlled hypothermia decreases the rate of metabolism in the brain. Slightly positive fluid balance should be maintained using crystalloid or colloid (hypertonic-hyperoncotic) solutions, at the same time maintaining cerebral perfusion pressure exceeding 70 mmHg. The treatment includes administration of antihypertensive medications, nonsteroidal antiinflammatory drugs, and barbiturates. Steroids decrease the permeability of capillaries and the hemato-encephalic barrier, promoting the movement of Na(+)/K(+) ions and water through the main endothelial membrane, and therefore they are used in the treatment of vasogenic cerebral edema as well as edema caused by a cerebral tumor. Glutamate and N-methyl-D-aspartate receptor antagonists improve cerebral microcirculation and metabolism. Trometamol corrects cerebral acidosis. Extended cerebral edema is treated surgically via a bilateral decompressive craniotomy, sometimes including craniotomy of lateral and posterior fossae. The treatment of cerebral edema is complex, and positive results may be expected only if the diagnosis and the provision of assistance are timely.

Effect of Edaravone, a Free Radical Scavenger, on Ischemic Cerebral Edema Assessed by Magnetic Resonance Imaging

The anti-edema effect of edaravone, a free radical scavenger, was evaluated by magnetic resonance imaging in six patients with extensive hemispheric ischemic stroke. T(2) relaxation time in the infarct core, the boundary zone of the infarct, and the noninfarcted hemisphere were calculated, and T(2) mapping was performed before and after edaravone administration. Edaravone administration significantly decreased the mean T(2) relaxation time in the boundary zone of the infarct from 121.5 +/- 9.2 (mean +/- standard deviation) to 114.5 +/- 9.9 msec (p = 0.008), but not in the core from 142.3 +/- 13.4 to 142.2 +/- 18.5 msec (p = 0.97) or the noninfarcted hemisphere from 93.0 +/- 3.7 to 93.1 +/- 3.8 msec (p = 0.91). The T(2) subtraction map clearly demonstrated shortened T(2) relaxation time in the boundary zone of the infarct. The present results indicate that edaravone can salvage the boundary zone of the infarct and is a useful cytoprotective anti-edema agent.

Taurine and the Relevance of Supplementation in Humans, in Health and Disease

Taurine, a beta-sulphur amino acid with a zwitterionic function, plays an important role in several biological processes. In humans taurine synthesis is limited. Therefore, intake by food is important. A normal diet, including animal products, contains a sufficient amount of taurine to provide the physiological necessary quantity of taurine. Taurine is a component of bile salts, which function as detergents for emulsification of dietary lipids and fat-soluble vitamins. Also, taurine is involved in the development of the brain and retina, which makes it an essential nutritional substrate in neonates and small children, who are limited in the synthesis of taurine. Moreover, taurine can act as an osmoregulator and antioxidant, which makes it an important amino acid during pathological conditions such as ischemic reperfusion injury, inflammation and brain oedema. Its osmolytic function helps to prevent alteration in the intra-cellular concentrations of all substances. In many models of oxidant-induced injury, taurine was shown to be tissue-protective as a non-toxic endogenous antioxidant. This review focuses on the biological actions of taurine, to illuminate possible clinical benefits of taurine. Keywords: Taurine, amino acid, supplementation, bile, osmoregulation, antioxidant

Intravitreal steroids in the management of macular oedema

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

Vitrectomy Seems to be Beneficial for Advanced Diffuse Diabetic Macular Oedema not Responding to Laser Treatment

To evaluate the surgical efficacy of vitrectomy, with optical coherence tomography, in patients with non-ischemic and ischemic diffuse diabetic macular oedema not responding to laser treatment. Ten eyes from nine patients (aged 46.0 +/- 20 years, diabetes duration 12.4 +/- 4 years) operated with vitrectomy for diabetic macular oedema not responding to laser treatment were evaluated before and 6 months postoperatively. Retinal thickness was assessed with optical coherence tomography, OCT, measuring the mean values of the centre of fovea and the second and third concentric rings from foveola. Four patients with type 1 diabetes had ischemic and five patients (6 eyes) with type 2 diabetes had non-ischemic diffuse macular oedema diagnosed on fluorescein angiography (FA). All eyes had an attached vitreous diagnosed on OCT. Mean foveal thickness for the three concentric rings from centre and out was significantly less 6 months postoperatively 437 +/- 125 vs. 286 +/- 67 microm; p = 0.027, 426 +/- 105 vs. 308 +/- 35 microm; p = 0.019 and 404 +/- 69 microm vs. 318 +/- 29 microm; p = 0.011 respectively. The decrease in foveal thickness was similar for eyes with and without signs of ischemic maculopathy. There was a trend toward improved visual acuity (VA) 6 months after surgery 0.4; range 0.2-0.6 compared to 0.3; range 0.1-0.5 before vitrectomy; p = 0.107). Vitrectomy seems to be a beneficial treatment for both ischemic and non-ischemic advanced diffuse diabetic macular oedema not responding to laser treatment.

Early Ischemic Edema on Cerebral Computed Tomography: Its Relation to Diffusion Changes and Hypoperfusion within 6 h after Human Ischemic Stroke

Background: Brain tissue hypoattenuation on early computed tomography is frequently included in decision making in acute stroke management. However, its pathophysiological counterpart needs further evaluation. Methods: By comparative imaging with diffusion-weighted imaging and ¹⁵O-water positron emission tomography we aimed to interpret early (<6 h) hypoattenuation. Results: In 11 patients, the hypoattenuation corresponded to a decreased proton diffusion (median 115.9% relative DWI value) measured by magnetic resonance imaging and to a severe hypoperfusion (below 12 ml/100 g/ min) assessed by positron emission tomography. The volume of parenchymal hypoattenuation correlated to the tissue with disturbed diffusion (Spearman’s rho = 0.73), but largely underestimated the hypoperfusion below 20 ml/100 g/min. Conclusions: Early hypoattenuation reflects the coupling of the severity of ischemia and resulting diffusion changes. It allows an estimate of the infarct core but underestimates the penumbral hypoperfusion.

Intravitreal Triamcinolone for the Treatment of Ischemic Macular Edema Associated With Branch Retinal Vein Occlusion

To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for ischemic macular edema associated with branch retinal vein occlusion (BRVO) and foveal ischemia. Prospective interventional case series. setting: Clinical practice. study population: Eighteen eyes of 18 patients with macular edema associated with BRVO and foveal ischemia. intervention: Four mg IVTA. main outcome measures: Visual acuity (VA), optical coherence tomography, macular thickness measurements, and treatment-related complications. The mean duration of BRVO before treatment was 14 months. All patients were followed for a minimum of nine months, and 12 patients completed 12 months follow-up. The mean logarithm of the minimum angle of resolution (logMAR) VA improved significantly from 0.81 +/- 0.36 at baseline to 0.65 +/- 0.30 at one month (P = .03) but did not vary significantly from baseline at three, six, nine, and 12 months. Macular thickness improved significantly in all eyes from a mean of 400 +/- 134 mum preinjection, to 228 +/- 58 mum at one month (P < .01) and 256 +/- 121 mum at three months (P < .01) but did not vary significantly from baseline at six, nine, and 12 months. Eight eyes developed posterior subcapsular cataract, intraocular pressure (IOP) exceeded 21 mm Hg in four eyes, and two eyes developed vitreomacular traction during follow-up. IVTA is effective in reducing ischemic macular edema associated with BRVO and foveal capillary nonperfusion. This reduction is often associated with a temporary improvement in VA. Raised IOP and development of posterior subcapsular cataract are disadvantages of this treatment.

Experimental stroke: ischaemic lesion volume and oedema formation differ among rat strains (a comparison between Wistar and Sprague–Dawley rats using MRI)

Investigating focal cerebral ischaemia requires animal models that are relevant to human stroke. This study was designed to evaluate the influence of early reperfusion and choice of rat strains on infarct volume and oedema formation. Thirty-six Wistar and Sprague-Dawley rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance imaging (MRI). Impact of rat strains: Reperfusion led to significant larger ischaemic lesion volumes in Wistar rats as compared to Sprague-Dawley rats (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led to significantly larger ischaemic lesion volumes in Sprague-Dawley rats (P<0.05). Oedema formation, however, was significantly more accentuated in Wistar rats (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in ischaemic lesion volume in Wistar rats. Oedema formation, however, was significantly reduced (P<0.0005). In Sprague-Dawley rats, reperfusion caused a significant reduction of ischaemic lesion volume (P<0.00005), but did not modify oedema formation. These findings emphasize the critical importance of rat strain differences in experimental stroke research.

Visual Acuity in Central and Branch Vein Retinal Occlusion in the Presence of Macular Edema: 1 Year of Follow-Up

One year after laser treatment of 117 eyes with central or branch retinal vein occlusion in the presence of macular edema, visual acuity was equally improved in the central retinal vein occlusion laser-treated and branch retinal vein occlusion non-laser-treated eyes. We concluded that fluorangiographically evident ischemic areas or significant macular edema are indications for laser therapy, and that a poor long-term functional prognosis is always related to more severe macular damage at the onset.

Inhibition of TWEAK Activity as a New Treatment for Inflammatory and Degenerative Diseases

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of structurally-related cytokines. TWEAK acts on responsive cells via binding to a cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK can regulate numerous cellular responses in vitro including cell proliferation, migration, survival, differentiation and apoptosis. TWEAK is also a proangiogenic and proinflammatory factor in vivo. Recent studies have indicated that pharmacological inhibition of TWEAK activity may have therapeutic efficacy in several diseases including ischemic stroke, cerebral edema, multiple sclerosis and rheumatoid arthritis. In this review we first introduce the TWEAK-Fn14 signaling system and then focus on the potential therapeutic utility of soluble Fn14-Fc fusion proteins and TWEAK neutralizing antibodies.

Differenzialdiagnosen des Knochenmarködems am Kniegelenk

Bone marrow edema of the knee joint is a frequent clinical picture in MR diagnostics. It can be accompanied by symptoms and pain in the joint. Diseases that are associated with bone marrow edema can be classified into different groups. Group 1 includes vascular ischemic bone marrow edema with osteonecrosis (synonyms: SONK or Ahlbäck's disease), osteochondrosis dissecans, and bone marrow edema syndrome. Group 2 comprises traumatic or mechanical bone marrow edema. Group 3 encompasses reactive bone marrow edemas such as those occurring in gonarthrosis, postoperative bone marrow edemas, and reactive edemas in tumors or tumor-like diseases. Evidence for bone marrow edema is effectively provided by MRI, but purely morphological MR information is often unspecific so that anamnestic and clinical details are necessary in most cases for definitive disease classification.

Glutamate release by neurons evokes a purinergic inhibitory mechanism of osmotic glial cell swelling in the rat retina: Activation by neuropeptide Y

Glial cell swelling is a central cause of ischemic edema in the brain and retina; however, the regulation of glial cell volume by endogenous factors in situ is largely unknown. In slices of the postischemic retina of the rat, the somata of glial (Müller) cells swell upon hypotonic stress that is not observed in slices of control retinas. We describe an endogenous signaling pathway that leads to inhibition of the osmotic glial cell swelling, and that is evoked by the release of glutamate from retinal neurons upon application of neuropeptide Y. Glutamate activates metabotropic glutamate receptors on swollen glial cells, which evokes a Ca2+ -independent purinergic signaling cascade that involves release of ATP, P2Y1 receptor activation, and transporter-mediated release of adenosine. Activation of A1 receptors causes the inhibition of osmotic glial cell swelling, by a protein kinase A-dependent activation of K+ and Cl- channels. It is proposed that the glutamate-evoked purinergic receptor signaling of glial cells is crucially involved in the cell volume homeostasis of the retina, and that this mechanism may contribute to the protective effect of adenosine in the ischemic tissue.

Abnormal Angiogenesis, Neurogenesis and Lymphangiogenesis in the Skin Underlies Delayed Wound Healing in the Sickle Mouse: Acceleration of Healing by Topical Opioids.

Chronic non-healing and painful leg ulcers are a serious manifestation of sickle cell disease (SCD). We hypothesized that structurally and functionally aberrant interdependent triad of angiogenesis, neurogenesis and lymphangiogenesis leads to localized ischemic insult, pain and edema, respectively, resulting in non-healing, painful and ulcerative wounds in SCD. We examined the dorsal skin of sickle mice with different severity (mild, NY1DD, medium, hBERK and severe, BERK) for blood vessels, sensory nerves and lymphatic vessels, by immunostaining 100 micron thick cryosections with endothelial specific anti-CD31, PGP9.5 and calcitonin gene related peptide (CGRP) and anti-lymphatic vessel endothelium marker LYVE-1, respectively. Z-series images were acquired using using laser scanning confocal microscopy. We observed a drastic difference in the structure, presentation and localization of all three processes in sickle mice as compared to their controls, which increased with the severity of the model. We found that, [i] epidermal thickening in BERK is 1/2 vs HbABERK (control expressing normal human Hb), [ii] majority of blood vessels localized in the sub-epidermal region in BERK vs dermal tissue in controls, [iii] microvasculature shows disorganization,tortuous, stringy and collapsed vessels in sickle, [iv] open lymphatic vessels arranged in parallel union with hair follicles in controls collapsed to 50 and 90% in diameter in mild and severe sickle models, respectively, while they moved by 90° becoming perpendicular to hair follicles in the severe sickle; [v] Peptidergic-immunoreactive nerve fibres increased with the severity of sickle state in the epidermis; and [vi] CGRP, a mediator in pain transmission is upregulated 2–5 times in sickle vs controls. These data suggest that aberrant, non-functional blood vessels lead to the development of localized hypoxia and ischemia resulting in tissue damage and compression of lymphatics which in turn increase edema and ulceration. Upregulated CGRP on peripheral nerves is suggestive of severe pain associated with sickle ulcers. Opioids interact with endothelium as well as nerves and promote angiogenesis and analgesia, respectively. Therefore, we examined the effect of topically applied opioids on healing of ischemic wounds in hBERK. In PBS treated HbABERK control, wound healing was 62% vs 42% in sickle on day 12 (p< 0.02). Complete wound closure was observed on day 19 in HbABERK, whereas, complete healing did not occur in sickle mice until 28 days. Topical application of morphine resulted in complete closure of wounds by days 14 and 23 in HbABERK and sickle mice, respectively. Similarly, hydromorphone stimulated complete wound closure as compared to 85% closure with PBS by day 23 in sickle (p<0.03). Blood and lymphatic vessel lengths were 20–35% higher in morphine or hydromorphone vs PBS-cream treated sickle wounds on days 13 and 28, respectively (p<0.05 PBS-Cream vs others on days 13 and 28). Thus wound repair is delayed in SCD due to aberrant vasculature and lymphatics and opioids stimulate normal angiogenesis and lymphangiogenesis which promote wound healing. We speculate that topical opioids may accelerate wound healing in painful non-healing leg ulcers in SCD.

Chronic administration of ethyl docosahexaenoate decreases mortality and cerebral edema in ischemic gerbils

Dietary docosahexaenoic acid (DHA) intake can decrease the level of membrane arachidonic acid (AA), which is liberated during cerebral ischemia and implicated in the pathogenesis of brain damage. Therefore, in the present study, we investigated the effects of chronic ethyl docosahexaenoate (E-DHA) administration on mortality and cerebral edema induced by transient forebrain ischemia in gerbils. Male Mongolian gerbils were orally pretreated with either E-DHA (100, 150 mg/kg) or vehicle, once a day, for 4 weeks and were subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. The content of brain lipid AA at the termination of treatment, the survival ratio, change of regional cerebral blood flow (rCBF), brain free AA level, thromboxane B 2 (TXB 2) production and cerebral edema formation following ischemia and reperfusion were evaluated. E-DHA (150 mg/kg) pretreatment significantly increased survival ratio, prevented post-ischemic hypoperfusion and attenuated cerebral edema after reperfusion compared with vehicle, which was well associated with the reduced levels of AA and TXB 2 in the E-DHA treated brain. These data suggest that the effects of E-DHA pretreatment on ischemic mortality and cerebral edema could be due to reduction of free AA liberation and accumulation, and its metabolite synthesis after ischemia and reperfusion by decreasing the content of membrane AA.

Hyperbaric oxygen reduces blood-brain barrier damage and edema after transient focal cerebral ischemia

Hyperbaric oxygen (HBO) has been shown to protect the brain parenchyma against transient focal cerebral ischemia but its effects on the ischemic microcirculation are largely unknown. We examined the potential of HBO to reduce postischemic blood-brain barrier (BBB) damage using repetitive MR-imaging and Na-Fluorescein uptake during 72 h of reperfusion and measured the effect of HBO on postischemic edema. Wistar rats and C57/Bl6 mice underwent focal ischemia for 2 h induced by filament occlusion of the middle cerebral artery (MCAO). Forty minutes after filament introduction, animals were placed in a HBO chamber and breathed either 100% O2 at 3.0 atmospheres absolute (ata; HBO group) or at 1.0 ata (control) for 1 h. In rats, MR-images were obtained 15 min after MCAO, and after 15 min, 3, 6, 24, 72 h of reperfusion. Volume of T1w postcontrast enhancement and an interhemispheric quotient of mean gray values (MGV) in T1w images were calculated for estimation of BBB damage. In ischemic mice, BBB permeability for Na-Fluorescein was measured fluoroscopically after 24 h of reperfusion. Physiological parameters and ischemic MR-perfusion did not differ between groups. Increased postischemic BBB permeability on postcontrast T1w images had a biphasic pattern and was located within the hyperintense areas on DWI and T2w images, respectively. HBO reduced volume of early and delayed BBB damage on postcontrast T1w images. Mean abnormal enhancing volumes at the various time points were at 15 min of reperfusion: 297 mm3 (control) vs. 196 mm3 (HBO); at 3 h: 3811 mm3 vs. 287 mm3; at 6 h: 4916 mm3 vs. 318 mm3; at 24 h: 5114 mm3 vs. 358 mm3; at 72 h: 9728 mm3 vs. 6817 mm3 (p<0.05 for 6, 24, 72 h). The quotient of MGV was significantly lower in the HBO treated animals at all time points: at 15 min of reperfusion: 1.730.11 (control) vs. 1.570.07 (HBO); at 3 h: 1.740.07 vs. 1.600.06; at 6 h: 1.770.07 vs. 1.620.06; at 24 h: 1.790.10 vs. 1.600.05; at 72 h: 1.810.10 vs. 1.620.07. Reduction of postischemic BBB damage by HBO was confirmed in mice. After 24 h of reperfusion, mean interhemispheric quotient (ischemic/nonischemic) of relative fluorescence units was significantly larger in control (1.560.50) than in HBO (1.110.16) treated mice. Effect of HBO on ischemic focal brain edema was estimated by two ways. First, volume of hyperintensity on T2w images, which represent both parenchymal damage and brain edema in the ischemic hemisphere, was significantly larger in control than in HBO treated animals at 72 h after MCAO. Second, on histological sections, volume attributable to focal edema was 7229 mm3 in the control and 4114 mm3 in the HBO group (p<0,05). In conclusion, early administration of HBO reduces rapid and delayed BBB damage and brain edema after transient focal cerebral ischemia. The molecular and cellular targets of this HBO effect and its potential implications for reduction of secondary microvascular complications are currently under investigation.