Regional mild hypothermia in the protection of the ischemic brain

Objective: To demonstrate that mild hypothermia can be a protective element when an ischemic onset occurs in rabbit brains. Methods: A rabbit model of focal ischemia was used to test the protection provided by mild hypothermia regionally produced by means of the placement of ice bag on the scalp of a hemicranium which has had previously its bone removed. Twenty New Zealand White rabbits were divided into two groups as follows: (A) a control group where an ischemic lesion was produced by coagulation of the middle cerebral artery and (B) a brain protected group where mild hypothermia was provided during 80 to 100 minutes after the same ischemic lesion. The brains slices were stained with 2,3,5-Triphenyletrazolium (TTC). The sections were photographed with a digital camera and the infarct volume was measured through a computer program. Results: The average of infarct volume was 70.53 mm³ in the control group. In the protected group, the average of infarct volume was 41,30 mm³ only in five animals. Five animals of this group did not demonstrate macroscopically and microscopically infarct area. Conclusions: We concluded that mild hypothermia regionally produced may protect ischemic brains of rabbits.

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Abstract WP259: Metabolomic Analysis of Ischemic Brain Tissue to Explore Specific Metabolic Pathway Assosiated With Cerebral Ischemia

Stroke ◽

10.1161/str.47.suppl_1.wp259 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Yusuke Yamamoto ◽

Kohkichi Hosoda ◽

Yasuhiro Irino ◽

Jun Tanaka ◽

Taichiro Imahori ◽

...

Keyword(s):

Cerebral Ischemia ◽

Western Blot ◽

Brain Tissue ◽

Water Soluble ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Acute Ischemia ◽

Rt Pcr ◽

Ischemic Lesion ◽

Ischemic Brain

Objectives: We investigated metabolic profiles of brain tissue in middle cerebral artery occlusion (MCAO) model of rats to explore the specific changes associated with acute ischemia. Methods: Focal cerebral ischemia was induced in rats using filament occlusion of the MCA. Tissue samples from the ischemic lesion were collected before and after ischemia(0, 30, 60, 120min, n=7-10). Sham operated rats were treated in the same way except MCAO (n=10). Water-soluble metabolites were extracted and analyzed using gas-chromatography/mass-spectrometry(GS/MS). The obtained data were analyzed by multivariate statistics to explore metabolic pathways associated with ischemia. The associated metabolic enzymes were investigated with RT-PCR and Western blot. Results: About ninety metabolites were identified by GC/MS. Principal component analysis and heatmap demonstrated clear separation between ischemia and control group (Figures). The most significant changes were decrease of fructose-6-phosphate and ribulose-5-phosphate, increase of hydroxybutyrate, and increase of GABA with time. These results suggested acceleration of pentose phosphate pathway to increase NADPH, upregulation of keton metabolism and neuroprotection by GABA. RT-PCR and Western blot did not indicate significant changes of transcription and protein level of the enzymes involved in these pathways and suggested changes of the enzyme activity by modification after transcription or translation such as phosphorylation. Conclusions: These results suggested the presence of neuroprotective metabolic change in the ischemic brain.

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BAG S53P4 putty as bone graft substitute – a rabbit model

Biomedical glasses ◽

10.1515/bglass-2017-0003 ◽

2017 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Ilkka Saarenpää ◽

Patricia Stoor ◽

Janek Frantzén

Keyword(s):

Bone Formation ◽

Bone Regeneration ◽

Proximal Tibia ◽

Rabbit Model ◽

Bone Graft Substitute ◽

Control Group ◽

The Novel ◽

Bone Augmentation ◽

New Bone Formation ◽

New Zealand White Rabbits

AbstractBioactive glass (BAG) S53P4 granules represent a bone augmentation biomaterial for the surgical treatment of bony defects, even in challenging conditions such as osteomyelitis. The aim of this eight-week rabbit implantation study was to evaluate the biocompatibility and bone regeneration performance of a BAG S53P4 putty formulation following its implantation into the proximal tibia bone of twenty-eight New Zealand white rabbits. BAG S53P4 putty was compared to BAG S53P4 granules (0.5-0.8 mm) to evaluate whether the synthetic putty binder influences the bone regeneration of the osteostimulative granules. The putty formulation facilitates clinical use because of its mouldability, injectability and ease of mixing with autograft. Implantation of putty and granules into proximal tibia defects resulted in good osseointegration of the two groups. Both biomaterials were biocompatible, showed high new bone formation, high vascularization and periosteal growth. No signs of disturbed bone formation were observed due to the PEG-glycerol binder in the BAG S53P4 putty. Instead, intramedullary ossification and stromal cell reaction were more advanced in the putty group compared to the control group (p = 0.001 and p < 0.001). In conclusion, the novel mouldable BAG S53P4 putty showed reliable bone regeneration in bony defects without adverse tissue or cell reactions.

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Abstract W MP81: Excess Salt Increases Infarct Size Produced by Photothrombotic Middle Cerebral Artery Occlusion Without Increasing Blood Pressure in Spontaneously Hypertensive Rats

Stroke ◽

10.1161/str.45.suppl_1.wmp81 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Hiroshi Yao ◽

Toru Nabika

Keyword(s):

Infarct Size ◽

Brain Tissue ◽

Infarct Volume ◽

Artery Occlusion ◽

Control Group ◽

Salt Loading ◽

Ischemic Brain ◽

Spontaneously Hypertensive ◽

Ischemic Brain Tissue ◽

Cerebral Artery Occlusion

Background and Purpose: Cerebral circulation is known to be vulnerable to excess salt (e.g., impaired vasodilation, increased oxidative stress, accelerated spontaneous stroke, and enhanced blood-brain barrier [BBB] disruption). To our knowledge, however, no study has investigated the effects of excess salt on focal ischemic injury. Methods: After 14 days of salt loading or water, spontaneously hypertensive rats (SHR, Izumo strain, n=43) or normotensive Wistar-Kyoto rats (WKY, n=11) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO. Brain albumin and hemoglobin contents, as indices of BBB disruption, were determined with SELDI-TOF-MS in ischemic brain tissue. Effects of excess salt on the lower limits of cerebral blood flow (CBF) autoregulation were also determined. Results: Two-way analysis of variance confirmed a significant effect of saline on the volumes of drinking in SHR (p=0.000). Resting mean arterial blood pressure (BP) in SHR was 137±15 (S.D.) mmHg and 141±7 mmHg in the salt loading and control groups, respectively. After MCAO, regional CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p=0.002), while albumin and hemoglobin levels in discrete brain regions were not different between the groups. In WKY, salt loading did not significantly increase infarct size. CBF response to hemorrhagic hypotension (i.e., autoregulation) was not affected by excess salt. Conclusions: We demonstrated that excess salt increased infarct size produced by photothrombotic MCAO without increasing BP in SHR but not in WKY. Excess salt did not deteriorate both vasogenic edema and hemorrhagic transformation of ischemic brain tissue after MCAO. The detrimental effects of excess salt were considered to be the result of compromised CBF in the ischemic brain tissue supplied by collateral circulation. A future study will investigate the mechanisms underlying the salt sensitivity to focal brain ischemia independent of BP changes.

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Effects of Zoledronic Acid on Physiologic Bone Remodeling of Condylar Part of TMJ: A Radiologic and Histomorphometric Examination in Rabbits

The Scientific World JOURNAL ◽

10.1155/2014/649026 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Ufuk Tatli ◽

Yakup Üstün ◽

Mehmet Kürkçü ◽

Mehmet Emre Benlidayı

Keyword(s):

Single Dose ◽

Zoledronic Acid ◽

Bone Remodeling ◽

Infusion Pump ◽

Rabbit Model ◽

Mandibular Condyle ◽

Control Group ◽

New Zealand White Rabbits ◽

Base Data ◽

Experimental Group

Objective. The purpose of the present study is to evaluate the effects of systemically administered zoledronic acid (ZA) on the physiological bone remodeling and the microarchitectural parameters of the condylar part of TMJ in a rabbit model.Study Design. Thirty skeletally mature male New Zealand white rabbits were randomly divided into two groups. The experimental group was administered an intravenous, single dose of 0.1 mg/kg ZA diluted with 15 mL of saline in a 15-minute perfusion with an infusion pump. The control group was administered only saline infusion for 15 minutes. All rabbits were sacrificed on the 21st postoperative day. Radiodensitometric and histomorphometric examinations were performed on the harvested mandibular condyles. The data were analyzed statistically.Results. Radiodensitometric findings showed that ZA treatment resulted in a significant increase in the mineralization of mandibular condyle. This result was supported by the histomorphometric findings.Conclusion. The present study has revealed that a temporary delay in the physiological bone remodeling using single dose of ZA increases bone mineral content and makes the microarchitecture of the mandibular condyle more compact. These effects may be regarded as base data and considered in numerous clinical situations including TMJ.

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Effect of UVA1 on hypertrophic scarring in the rabbit ear model

Bioscience Reports ◽

10.1042/bsr20190007 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Tong Zhang ◽

Zhiming Shen ◽

Jie Zheng ◽

Rui Jiang

Keyword(s):

New Zealand ◽

Rabbit Model ◽

Tissue Growth ◽

Control Group ◽

High Dose ◽

Hypertrophic Scarring ◽

Dermal Thickness ◽

New Zealand White Rabbits ◽

Uva1 Phototherapy ◽

The Impact

Abstract Hypertrophic scars (HTSs) are common and cause functional and psychological morbidity. UVA1 (340–400 nm) phototherapy has been previously shown to be effective in the treatment of localized scleroderma, systemic sclerosis, and POEMS syndrome with minimal side effects, all of which are presented as collagen fibrils hyperplasia that is common with scarring in skin histology. In the present study, we aimed to investigate the impact of UVA1 on the protein expression of TGF-β signal pathway and myofibroblasts in a rabbit model of cutaneous scarring. Full-thickness skin wounds (2 cm × 5 cm in diameter) were made in New Zealand white rabbits to establish the hypertrophic scarring model. New Zealand white rabbits were divided into two treatment groups (n=30 wounds per group with an equal number of controls): medium-dose of UVA1 phototherapy group: 60 J/cm2; high-dose of UVA1 phototherapy group: 110 J/cm2. Left ears were used for treatment and the right ones were used for control. Treatment was administered five times weekly for 6 weeks. Treated and untreated control wounds were harvested at various time points and examined by histologic examination, immunohistochemical assessment, and ultrastructural evaluation. The results showed that UVA1 phototherapy caused a significant reduction in dermal thickness by histological features, whereas the scar index was descended significantly in both medium- and high-dose UVA1 groups compared with the control group. Examination of immunohistochemistry also revealed a marked suppression of tissue growth factor-β (TGF-β) (both medium- and high-dose), α smooth muscle actin (α-SMA) (only high-dose), and tissue inhibitor of metalloproteinase 1 (TIMP-1) (only high-dose), and apparent increase in matrix metalloproteinases (MMP-1) (both medium- and high-dose) compared with the control. The ultrastructural evaluation showed the collagen fibers’ diameter had shrunk, and that fibroblastic cytoplasm was not affluent and in a quiescent stage. These findings of the present study suggested that administration of UVA1 irradiation is effective to improve the experimental HTS model and raises a possibility of the therapeutic approach of UVA1 in the scar. Although not directly examined in the present study, MMP inhibition is hypothesized to be responsible for this effect. However, early UVA1 treatment could not prevent the formation of scar model.

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Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp116 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Ifechukwude Joachim Biose ◽

Katie E Salmeron ◽

Anthony Parker ◽

Ann Stowe ◽

Gregory Bix

Keyword(s):

Physical Activity ◽

Ischemic Stroke ◽

Infarct Volume ◽

Exercise Group ◽

Artery Occlusion ◽

Control Group ◽

Lesion Volume ◽

Ischemic Lesion ◽

Voluntary Physical Activity ◽

Wheel Activity

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.

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A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-128 ◽

1990 ◽

Vol 68 (7) ◽

pp. 845-850 ◽

Cited By ~ 8

Author(s):

C. Tissa Kappagoda ◽

Alan B. R. Thomson ◽

Manohara P. J. Senaratne

Keyword(s):

Rabbit Model ◽

Rabbit Aorta ◽

Control Group ◽

Standard Diet ◽

Cholesterol Feeding ◽

High Cholesterol ◽

Experimental Animals ◽

New Zealand White Rabbits ◽

Experimental Group ◽

Endothelium Dependent Relaxation

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (−9.0 to −5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (−6.0 log mol/L) was significantly (p < 0.05) impaired in the experimental group (34.3 ± 3.8%) compared with that in the control group (79.8 ± 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 ± 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 ± 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.Key words: atherosclerosis, endothelium-dependent relaxation, rabbit aorta, regression.

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The relationship of oxidative stress parameters with infarct volume and National Institutes of Health Stroke Scale in ischemic stroke / İskemik inmede oksidatif stres parametrelerinin infarkt volümü ve National Institutes of Health Stroke Scale ile ilişkisi

Turkish Journal of Biochemistry ◽

10.1515/tjb-2015-0013 ◽

2015 ◽

Vol 40 (4) ◽

Author(s):

Ferhat İçme ◽

Özcan Erel ◽

Zeynep Saral Öztürk ◽

Tolga Öz ◽

Akkan Avci ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Infarct Volume ◽

National Institutes Of Health ◽

Control Group ◽

Case Group ◽

Ischemic Lesion ◽

Oxidative Stress Parameters ◽

The Relationship ◽

Stress Parameters

AbstractObjective: What we know about the relationship between oxidative stress parameters and ischemic stroke is still limited and controversial. Our study aimed to investigate the relationships among ischemic lesion volume, National Institutes of Health Stroke Scale (NIHSS) values, and oxidant and antioxidant levels to determine whether oxidative stress paramaters is effective on stroke severity in ischemic stroke patients.Methods: The study included 34 patients with ischemic stroke and 34 volunteers with no active diseases. Total Oxidant Status (TOS), Total Antioxidant Status (TAS), thiol, paraoxonase, stimulated paraoxonase (stparaoxonase) and arylesterase were measured in blood samples collected on admission from patients diagnosed with ischemic stroke. The Oxidative Stress Index (OSI) was calculated. The same oxidative stress parameters were measured in the control group and compared with the patient group. Correlation between the oxidative stress parameters, the infarct volume and the NIHSS was studied. NIHSS was calculated when patients were admitted to the emergency department. The infarct volume was calculated using diffusion-weighted magnetic resonance imaging performed in the first 72-96 hours.Results: TOS and OSI values were significantly higher in the case group than the control group. Paraoxonase, arylesterase, and thiol values were significantly lower in the case group than the control group. TAS and stparaoxonase values weren’t differed significantly between the case and control groups. There were significant negative correlations between the NIHSS value and both the paraoxonase value and stparaoxonase value. There were no significant correlations between the NIHSS value and the infarct volume and the TAS, TOS, OSI, arylesterase, and thiol values.Conclusion: We concluded that change in oxidative stress balance in favor of oxidants could be a cause in the pathogenesis of ischemic stroke but oxidative stress alone can’t be sufficient in predicting the severity of stroke.

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A metabolic profiling analysis of degenerative intervertebral disc disease in a rabbit model via GC/TOF-MS

10.21203/rs.2.17337/v1 ◽

2019 ◽

Author(s):

Xiaolin Wu ◽

Hongfei Xiang ◽

Guoqing Zhang ◽

Yougu Hu ◽

yan wang ◽

...

Keyword(s):

New Zealand ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Rabbit Model ◽

Intervertebral Discs ◽

Control Group ◽

Model Group ◽

New Zealand White Rabbits ◽

Tof Ms

Abstract Background: To establish an analytical method for studying intervertebral disc metabolomics based on gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Methods: To establish a rabbit model of intervertebral disc degeneration, the intervertebral discs of six New Zealand white rabbits were punctured. GC/TOF-MS was applied to analyze degenerated discs of the six model group animals and six similar New Zealand white rabbits considered as the control group. Pattern recognition and nonparametric test analyses were utilized to evaluate the data as well as screen for and identify significant biomarkers. Metabolites and metabolic pathways relevant to associated pathological processes were studied. Results: We established a rabbit model of intervertebral disc degeneration and an orthogonal partial least squares-discriminant analysis (OPLS-DA) disease-distinguishing model of intervertebral disc degeneration for contrast against the typical physiological state of intervertebral discs. Expression of six metabolites in degenerated and normal intervertebral discs of New Zealand white rabbits was evaluated. Levels of four metabolites expressed in the model group were significantly higher than in the control group, while two other metabolites were expressed at significantly lower levels in the model group as compared to the control group. Conclusions: This paper demonstrates that metabolic profiling of both degenerated and normal intervertebral rabbit discs is a feasible method of metabolomic analysis. Via in-depth filtering of characteristic metabolites, we found a high correlation between metabolic variations and intervertebral disc degeneration. Further studies on endogenous metabolites and pathways involved in intervertebral disc degeneration will provide a better understanding of associated molecular mechanisms and lay foundations for effective clinical treatment.

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Study of the Soil—Plant (Carrot)—Animal Cycle of Nutritive and Hazardous Minerals in a Rabbit Model

Acta Veterinaria Hungarica ◽

10.1556/004.47.1999.2.4 ◽

1999 ◽

Vol 47 (2) ◽

pp. 181-190 ◽

Cited By ~ 6

Author(s):

A. Bersényi ◽

S. Fekete ◽

I. Hullár ◽

I. Kádár ◽

M. Szilágyi ◽

...

Keyword(s):

Crude Protein ◽

Dry Matter ◽

Rabbit Model ◽

Basal Diet ◽

The Body ◽

High Concentration ◽

New Zealand White Rabbits ◽

Heavy Metal Salts ◽

Experimental Treatments ◽

Rate Of Accumulation

Carrots were grown on soils polluted by heavy metal salts. Each particular microelement reached a high concentration [molybdenum (Mo) 39.00, cadmium (Cd) 2.30, lead (Pb) 4.01, mercury (Hg) 30.00, and selenium (Se) 36.20 mg/kg dry matter] in the carrot. In a metabolic balance trial conducted with 15 male and 15 female New Zealand White rabbits, the control animals (n = 5) were fed ad libitum with concentrate as basal diet, while the other rabbits received the basal diet and carrots containing the particular microelement. Blood samples were taken to determine the activity of serum enzymes. To investigate the metabolism of Mo, Cd, Pb, Hg and Se, samples were taken from the heart, liver, lungs, kidneys, spleen, ovaries/testicles, entire digestive tract, adipose tissue, femur, hair, faeces and urine. Carrot had significantly higher digestibility for all nutrients than the rabbit concentrate. Carrot samples of high Pb content had the lowest digestibility of crude protein. The microelements differed in their rate of accumulation in the organs examined: Mo and Cd accumulated in the kidneys, Pb in the kidneys, liver, bones and lungs, Hg in the kidneys and liver, while Se in the liver, kidneys and heart. The proportions of microelements eliminated from the body either via the faeces and urine (Mo 80.18% and Se 47.41%) or via the faeces (Cd 37.86%, Pb 66.39%, Hg 64.65%) were determined. Pathohistological examination revealed that the rate of spermatogenesis was reduced in the Mo, Cd, Pb and Hg groups compared to the control. Lead, Cd and Hg intake resulted in a considerable decrease in gamma-glutamyltransferase (GGT) and in an increase of alkaline phosphatase (ALP) activity because of damages to the kidneys and bones. All experimental treatments decreased the activity of cholinesterase (CHE) because of lesions in the liver.

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