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PubMed1976

[Maxillary artery to middle cerebral artery anastomosis in dog-- a new experimental model (author's transl)].

End-to-side anastomosis between the maxillary artery and a branch of the middle cerebral artery was performed in the dog. The technique was devised as a new experimental model for extracranial-intracranial arterial shunt operation. The middle cerebral artery was ligated at the origin through a subtemporal small burr hole under the operating microscope in 13 dogs. Then, the shunt operation was carried out in 8 dogs 4 hours after the ligation(acute state), and in 5 dogs 3 weeks after(chronic stage). The patency of the anastomotic site was evaluated by the selective external carotid angiography 2 weeks after the shunt operation. In the acute stage of 8 dogs, 7 cases showed patency of anastomosis (88%), and in the chronic stage of 5 dogs, arteriogram revealed 4 patent anastomosis (80%). In successful cases, arteriogram showed excellent filling of the entire territory of the middle cerebral artery through the shunts (Fig. 4, 5). Various types of experimental shunt operation were attempted in our review of the literature. Among them, the anastomosis between the superficial temporal artery and a branch of the middle cerebral artery by Yasargil (1967) is rather popular and this procedure has been used by some investigators including us to investigate the effect of the extracranial-intracranial shunt on experimental acute stroke. So far as dog's experiment is concerned, the superficial temporal artery appeared to be not suitable for a donor artery, because the superficial temporal artery runs far from the middle cerebral artery and its distal part is extremely small in caliber. Therefore, the superficial temporal artery was often obstructed by compression, kinking or narrowing by surrounding tissues and by adhesion to the bone edge of the burr hole. On the other hand, the maxillary artery of the dog, which is the largest terminal branch of the external carotid artery, has plenty of blood flow and suitable size for end-to-side anastomosis to the middle cerebral artery. In addition, maxillary artery is located very close to the proximal part of the middle cerebral artery. These anatomical and spatial advantage of the maxillary artery seemed to be favorable donor artery to the middle cerebral artery and have brought hight patency rate in our series of anastomosis than that of the other previous experimental extracranial-intracranial shunts. To our knowledge, this is the first report on successful patent shunt formation after long-term occlusion of the middle cerebral artery in animals. Now, it is in our mind that progress of the study can be expected in the field of extracranial-intracranial shunt operation for cerebral infarction by this experimental procedure.

Animals↗

PubMed1994

Gallium nitrate and spinal cord injury. A pilot study of efficacy using an experimental model.

Gallium (Ga) nitrate has been shown to attenuate immune-mediated tissue destruction in models of neurological autoimmunity. Based upon these observations, we evaluated the efficacy of Ga nitrate in attenuating the inflammatory response and modifying clinical recovery in an experimental model of traumatic spinal cord injury (SCI). Using a randomized, double-blind, placebo-controlled design, 12 adult female Sprague-Dawley rats received injections of either Ga nitrate (n = 8) or saline (n = 4) following experimental SCI. Ga treated animals received 30 mg/kg elemental Ga followed by weekly injections of 10 mg/kg elemental Ga. There were no observable differences between the Ga treated and the saline control groups using various behavioral paradigms examined during the study period. Histological and immunocytochemical data qualitatively showed no observable differences between Ga treated (n = 4) and control (n = 2) groups sacrificed 18 days following SCI. Although the efficacy of Ga in this pilot study of experimental SCI was not demonstrated, the potential of Ga to attenuate inflammatory-mediated reactions remains an exciting possibility in the area of SCI. Our preliminary results should not discourage future research endeavors in this regard. A more complete analysis of dose response, time and mode of Ga administration (preinjury or postinjury), and availability of Ga across the blood-brain barrier is needed to further evaluate the efficacy of this compound.

Animals↗

PubMed2006

17 beta-Estradiol may affect vulnerability of striatum in a 3-nitropropionic acid-induced experimental model of Huntington's disease in ovariectomized rats.

The aim of present study was to clarify the role of female sex hormones in the development and course of neurodegenerative disease in an experimental model of Huntington's disease induced by 3-nitropropionic acid (NPA) (30 mg/kg intraperitoneally (i.p.)/day for 4 days) in ovariectomized rat. Gonadectomy prompted oxidative stress and cell death evaluated by the detection of caspase-3, whereas 3-nitropropionic acid enhanced the oxidative stress induced by ovariectomy and it triggered cell damage characterized by increases of LDH levels. These changes were prevented by administration of 17 beta-estradiol. Our findings suggested that: (i) ovariectomy induced oxidative stress and apoptosis in the brain; (ii) 3-nitropropionic acid exacerbated oxidative stress induced by ovariectomy and shifting cell to cell death; and (iii) 17 beta-estradiol administration decreased oxidative stress and cell death induced by ovariectomy and 3-nitropropionic acid. These results revealed that sex ovarian hormones play a important role in onset and development of neurodegenerative diseases, as well as neuroprotective effects of 17 beta-estradiol against the changes induced ovariectomy and ovariectomy plus 3-nitropropionic acid.

Animals↗

PubMed2007

Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsy.

To characterize the type of interactions between vigabatrin (VGB) and tiagabine (TGB) -- two newer antiepileptic drugs influencing GABA-ergic neurotransmitter system, the isobolographic analysis was used in two experimental models of epilepsy: the maximal electroshock seizure threshold (MEST) test and pentylenetetrazole (PTZ)-induced seizures in mice. Results indicated that VGB and TGB administered separately (i.p.) increased the electroconvulsive threshold in mice, which allowed the calculation of their TID(20) values (threshold increasing doses by 20% over the threshold of control animals) in the MEST test. The TID(20) for VGB was 226.2 mg/kg and that for TGB was 4.4 mg/kg. With isobolography, the combinations of VGB with TGB (at fixed-ratios of 1:3, 1:1 and 3:1) exerted additive interactions in the MEST test in mice. Similarly, VGB and TGB injected separately (i.p.) suppressed the PTZ-induced seizures, and their ED(50) values (median effective doses, protecting 50% of the animals tested against clonic convulsions) for VGB and TGB were 622.5 mg/kg and 0.8 mg/kg, respectively. Isobolographic analysis of interactions revealed that the combinations of VGB with TGB at the fixed-ratios of 1:3 and 1:1 produced supra-additive (synergistic) interactions against PTZ-induced seizures. Only the combination of VGB with TGB at the fixed-ratio of 3:1 was additive in the PTZ test. The evaluation of acute adverse-effect potential for all fixed-ratio combinations of VGB with TGB (administered at their TID(20) and ED(50) values from the MEST and PTZ tests) revealed that none of the examined combinations affected motor coordination in the chimney test and altered neuromuscular tone in the grip-strength test in mice. In contrast, VGB in combinations with TGB produced the antinociceptive effects with respect to suppression of acute thermal pain in animals subjected to the hot-plate test. Based on this preclinical study, one can ascertain that the combination of VGB with TGB would provide an adequate seizure control in epileptic patients.

Animals↗

PubMed2003

Surgically induced unilateral pulmonary hypertension: time-related analysis of a new experimental model.

OBJECTIVE: Patients with irreversible pulmonary vascular obstructive disease caused by pulmonary hypertension due to congenital heart defects are considered either inoperable or only candidates to lung transplantation. This study evaluated an experimental model of surgically induced unilateral pulmonary hypertension. METHODS: In eight pigs, 2-months-old, the left pulmonary artery was divided at the origin and end-to-side anastomosed to the descending thoracic aorta through a left thoracotomy. In this way, increased pulmonary blood flow in the right lung and systemic perfusion pressure and oxygenation in the left lung were obtained. After an interval of 6-12 weeks the animals underwent cardiac catheterization and were then sacrificed. Histological examination was done on both the lungs. RESULTS: The mean left-to-right shunt through the left pulmonary artery diminished from 58.9+/-9.6% at the end of the procedure to 4.5+/-1.5% at the latest hemodynamic evaluation (P<0.01). Pressures and saturations remained identical in aorta and left pulmonary artery, without reduction (NS) with FiO(2)=1.0 ventilation; in the right pulmonary artery there was a mild elevation of the pressures, but still responsive (P<0.05) to FiO(2)=1.0 ventilation. Lung histology showed normal right pulmonary arteries, but irreversible vascular lesions like intimal fibrosis, medial hypertrophy, vascular occlusions, plexiform and dilatation lesions in all the left lungs. CONCLUSIONS: The lung exposed to systemic pressure and oxygenation develops irreversible vascular lesions typical of pulmonary vascular obstructive disease. The lung exposed to increased flow shows only mild elevation of the arterial pressure, remains responsive to oxygen vasodilatation, and displays normal histology.

Animals↗

PubMed2001

Experimental models of gram-negative sepsis.

BACKGROUND: The mortality rate from sepsis has improved little over the past two decades. One reason for this has been the use of flawed or inappropriate experimental models in preclinical sepsis studies. METHODS: A literature review of animal models of sepsis was performed following a Medline search based on the following medical subject headings: disease models, endotoxin, inflammation, peritonitis and sepsis. Additional references were identified from the papers identified in the search. RESULTS AND CONCLUSION: Many animal models of sepsis have been described but none has proved to be superior. Extrapolation of results from endotoxicosis or bacterial infusion models should be regarded with caution. Peritonitis models should be accepted as the 'gold standard' but the use of appropriate virulent bacterial species needs to be ensured. A standardized panel of animal models for the preclinical assessment of immunomodulatory agents should be established, including at least one immuno- suppressed model to simulate the immunocompromised patient with sepsis. A uniform and valid definition of sepsis applicable to both small and large animal species is required.

Animals↗

PubMed1986

Interpretation of traumatic lumbar puncture. A prospective experimental model.

Contamination of cerebrospinal fluid (CSF) with blood at the time of collection interferes with the interpretation of laboratory studies. Twenty-four children with normal CSF were studied prospectively using an experimental model. Blood was added to clear CSF, producing red cell counts from 1,000 to 600,000 cells per cubic millimeter. The expected values for white blood cell count, protein, percent neutrophils, and glucose were calculated, using the results from uncontaminated CSF, peripheral blood cell counts, blood protein, and the red blood cell count of the contaminated specimen. The ratio of observed values to expected values ranged from 0.13 to 3.00 for CSF white blood cell count (mean 0.96, standard deviation 0.56), from 0.55 to 1.63 for CSF protein (mean 0.97, standard deviation 0.23), and from 0.10 to 2.25 for percent neutrophils in the CSF (mean 1.17, standard deviation 0.41). CSF glucose was unchanged by the addition of blood. Guidelines for interpretation of laboratory studies following traumatic lumbar puncture are suggested.

Blood↗

PubMed1990

[Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart].

The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia.

Animals↗

PubMedDate not supplied

[Effect of position with respect to gravitational force on the hydrodynamics of an experimental model of saccular aneurysm].

We wish to confirm the hypothesis that the hydrodynamics of brain aneurysms depend partially on their position, with respect to the force of gravitation, and so developed an experimental model of latex aneurysms, which was subjected to a pulsatile flow. Four different registers were made with an injection of ink and radioisotopes. A physical model was designed which allowed a quantitative analysis of the results and which allows a mathematical analysis of the aneurysm's hydrodynamics. The results suggest that when an aneurysm is oriented against the force of gravity, it has a very low risk of thrombosis, and the scarce turbulence of the flow condition a lower risk of growth and rupture, in comparison with other conditions. The greatest flow turbulence against the wall is found in the aneurysm oriented downwards, that is parallel to the force of gravity. Due to its hydrodynamics, the downwards aneurysm has the highest probability of complication, since it has; a) higher risk of rupture due to the impact of the stream upon the wall and to the turbulence this impact produces, b) a higher risk of thrombosis produced by the circulatory stasis which has a dome. This combination of factors (rupture and thrombosis) allows these aneurysms to grow more than others.

Gravitation↗

PubMed1983

Experimental models of bacterial arthritis: a microbiologic and histopathologic characterization of the arthritis after the intraarticular injections of Neisseria gonorrhoeae, Staphylococcus aureus, group A streptococci, and Escherichia coli.

We report the first reproducible experimental model of gonococcal arthritis, utilizing the intraarticular injection of virulent strains of N. gonorrhoeae. An acute, purulent synovitis with a marked polymorphonuclear leukocyte infiltrate developed during the 1st 24 h and persisted for at least 72 h, followed by a more chronic, mononuclear, proliferative synovitis. The histopathologic characteristics of this acute, then chronic synovitis were comparable to that after the intraarticular injection of other bacteria. N. gonorrhoeae could not be recovered from the injected joints 24 h after their inoculation, whereas Staphylococcus aureus, hemolytic streptococci, and E. coli could be recovered for days to weeks after the intraarticular injection.

Animals↗

PubMed1980

Myocardial hypertrophy in the rat. Correlation between two experimental models.

Two different conditions responsible for cardiac hypertrophy in the rat were investigated: the first one is isoproterenol-induced myocardial infarct, the second is exposure to hypoxia (0.42 atmospheres/24 h) in hypobaric chamber. To demonstrate that in both experimental models stimulation of protein synthesis is an absolute requirement to induce cardiac hypertrophy, a variety of techniques were employed including: evaluation of dry heart weight value, concentration of radiothallium (201T1) in the heart and effects of inhibitors of protein synthesis (Puromycin). Experimental results have showed: (A) a significant increase (p<0.001 as compared to control group) of dry heart weight values both in isoproterenol-treated and hypoxic rats; (B) a significant increase over control group (p<0.001) in myocardial 201T1 concentration in isoproterenol-treated rats; (C) total inhibition of cardiac hypertrophy in Puromycin treated group subjected to hypoxia. Finally, on the basis of different mortality observed in infarcted (85.0%) or hypoxic (5.0%) rats treated with Puromycin (40 mg/Kg body weight i.p.) a different role of cardiac hypertrophy in 2 experimental conditions is postulated: in the case of infarct-like lesions the cardiac hypertrophy has compensatory significance; under hypoxic stimulus is only due to increased cardiac work.

Animals↗

PubMed1993

Histopathological assessment of tumoral destruction by alcoholization in an experimental model of human hepato-cellular carcinoma transplanted in nude mice.

This study aims to assess the efficacy of intra-tumoral alcoholization as a potential therapy against small hepatocellular carcinoma (HCC). The experimental model consisted of 20-mm diameter tumors resulting from subcutaneous abdominal injection of Hep G2 human hepatoma cell lines into nude mice (nu/nu). Alcoholization was performed using either a single centro-tumoral injection or multiple cross-shaped injections (tangential and oblique), during one sequence with a total dose of 0.1, 0.2 or 0.3 ml of 95% ethanol. Efficacy was assessed by the percentage of tumoral necrosis using a semi-quantitative method. Fifty-four tumors were alcoholized. Forty-eight hours following alcoholization, the tumor was regularly replaced by a necrotic ulcer. A single centro-tumoral injection always resulted in the persistence of a small peripheral edge of tumor cells even with the highest dose used (no dose-related effect). By contrast, the use of multiple injections restored a dose-related effect. Oblique cross-shaped injections of 0.3 ml of ethanol resulted in the highest mean tumoral necrosis rate (m +/- SD = 99 +/- 1%; range = 97-100). This study confirms that alcoholization is an efficient way to destroy hepatocarcinoma tissue and suggests that ethanol diffusion in HCC is less than 20 mm. In addition it demonstrates that increasing number and location of injections restores a dose-related effect, while efficacy is improved using oblique injections.

Animals↗

PubMed2005

Mechanisms and experimental models of chronic obstructive pulmonary disease exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity, mortality, and rising health care costs. In addition, they are associated with an accelerated loss of lung function and thus have a direct effect on disease progression. There are few studies examining the cellular and molecular mechanisms of COPD exacerbations. Exacerbations are linked to increased airway inflammation and oxidative stress, but many questions remain unanswered regarding the key inflammatory cells and mediators. Current therapies for COPD exacerbations are of limited effectiveness, and a better understanding of the inflammatory events at exacerbation is required to devise new therapeutic agents. The development of experimental models of exacerbation-for example, the use of experimental rhinovirus infection in humans with COPD-would greatly facilitate studies of exacerbations.

Acute Disease↗

PubMed1992

Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies.

OBJECTIVE: To determine whether anti-Ro/SS-A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization. METHODS: An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed. RESULTS: Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti-La/SS-B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti-native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produced alterations in membrane repolarization. CONCLUSION: Anti-Ro/SS-A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus.

Action Potentials↗

PubMed2002

Effect of dietary supplementation with vitamin D metabolites in an experimental model of turkey osteomyelitis complex.

Supplementation with vitamin D3 was previously shown to protect Escherichia coli challenged birds that underwent two dexamethasone (DEX) treatments at 5 and 12 wk of age in an experimental model of turkey osteomyelitis complex (TOC). The purpose of the present study was to determine the effects of dietary supplementation with 10 microg of 1,25 dihydroxyvitamin D3 (1,25D)/ kg feed or 99 microg of 25-hydroxyvitamin D3 (25D)/kg feed on disease resistance in the same model. Birds were fed the supplemented diets continuously and ad libitum. Seven hundred twenty turkey poults were placed into 24 floor pens in a 3 x 2 x 2 design (three vitamin D treatments, two DEX treatments, two E. coli treatments, with two replicate pens per treatment). At 5 wk of age, half of the birds were treated with DEX, and half of the DEX-treated birds and half of the nontreated birds were challenged with E. coli. All mortalities and lame birds were necropsied. At 9 wk, all of the DEX- or E. coli-treated birds were given another series of DEX injections; 2 wk later 10 birds per pen were necropsied. At 12 wk, survivors of the previous challenges were given a third DEX treatment, and all birds were necropsied 2 wk later. After the first series of DEX injections, mortality was increased in the 25D-supplemented birds that were given the DEX treatment and the E. coli challenge. After the second series of DEX injections, the main effect mean BW was significantly lower in birds given 1,25D as compared to controls and 25D-supplemented birds. Mortality was higher in 1,25D-supplemented birds that were challenged with E. coli at 5 wk and treated with DEX at 9 wk as compared to 25D-supplemented birds. The 1,25D-treated birds that were treated with DEX at 5 and 9 wk and challenged with E. coli at 5 wk had higher mortality and air sacculitis scores as compared to controls and 25D-treated birds. The main effect mean mortality was significantly higher in birds given 1,25D as compared to controls and 25D-treated birds. The percentage of birds with TOC lesions was decreased from 27% to 0 by 25D and 1,25D in the groups given two DEX treatments and E. coli challenge. After the third DEX treatment, BW of 1,25D-suppplemented birds was decreased, and mortality and air sacculitis scores were increased. Bone strength was generally increased by supplementation with 1,25D, whereas 25D supplementation increased bone strength only in birds challenged at 5 wk and treated with DEX at Weeks 9 and 12. In this study, supplementation with vitamin D metabolites decreased TOC incidence in E. coli-challenged birds given two DEX treatments. However, toxic effects were observed in most supplemented DEX-treated birds and may be attributed to an additive effect of DEX treatment, E. coli septicemia, and vitamin D supplementation.

Animal Nutritional Physiological Phenomena↗

PubMed2004

Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea-pigs.

BACKGROUND: Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti-inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen-induced chronic airway inflammation in guinea-pigs (GP). METHODS: GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol. RESULTS: Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025). CONCLUSION: Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration.

Acetates↗

PubMed1996

Experimental models of accelerated atherosclerosis syndromes.

The processes of angioplasty restenosis, vein graft failure, and transplant atherosclerosis, collectively termed 'syndromes of accelerated atherosclerosis', have been the focus of significant clinical and experimental research. Limitations of clinical studies have forced emphasis onto experimental animal models for the purpose of determining pathophysiology and evaluation of potential therapeutic strategies. However, the apparent failure of many in vivo animal models to predict interventional outcome in humans has raised doubt over their suitability as models of these pathophysiological states. Similar criticism has befallen the use of in vitro techniques for elucidating pathophysiology of the cellular elements. An awareness of the shortcomings of the various experimental models in use would therefore seem prerequisite both to a more critical evaluation of data generated from their use, and to the development of truly effective therapeutic strategies for humans.

Animals↗

PubMed1999

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical.

BACKGROUND: A study was carried out to investigate the effect of two antioxidants--Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)--in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. METHODS: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 microliters of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n = 8) did not receive any treatment and served as a positive control. Groups 2 (n = 8) and 3 (n = 8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n = 4) was treated by three intramuscular injections of 15,000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. RESULTS: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. CONCLUSION: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Administration, Oral↗