Ultrasound-assisted convection-enhanced delivery to the brain in vivo with a novel transducer cannula assembly

2012 ◽  
Vol 117 (6) ◽  
pp. 1128-1140 ◽  
Author(s):  
George K. Lewis ◽  
Zachary R. Schulz ◽  
Susan C. Pannullo ◽  
Teresa L. Southard ◽  
William L. Olbricht
Keyword(s):  
Continuous Wave ◽  
Sprague Dawley ◽  
Convection Enhanced Delivery ◽  
Rodent Brain ◽  
Sprague Dawley Rats ◽  
Ultrasound Assisted ◽  
Group 2 ◽  
The Brain ◽  
Group 1

Object In convection-enhanced delivery (CED), drugs are infused locally into tissue through a cannula inserted into the brain parenchyma to enhance drug penetration over diffusion strategies. The purpose of this study was to demonstrate the feasibility of ultrasound-assisted CED (UCED) in the rodent brain in vivo using a novel, low-profile transducer cannula assembly (TCA) and portable, pocket-sized ultrasound system. Methods Forty Sprague-Dawley rats (350–450 g) were divided into 2 equal groups (Groups 1 and 2). Each group was divided again into 4 subgroups (n = 5 in each). The caudate of each rodent brain was infused with 0.25 wt% Evans blue dye (EBD) in phosphate-buffered saline at 2 different infusion rates of 0.25 μl/minute (Group 1), and 0.5 μl/minute (Group 2). The infusion rates were increased slowly over 10 minutes from 0.05 to 0.25 μl/minute (Group 1) and from 0.1 to 0.5 μl/minute (Group 2). The final flow rate was maintained for 20 minutes. Rodents in the 4 control subgroups were infused using the TCA without ultrasound and without and with microbubbles added to the infusate (CED and CED + MB, respectively). Rodents in the 4 UCED subgroups were infused without and with microbubbles added to the infusate (UCED and UCED + MB) using the TCA with continuous-wave 1.34-MHz low-intensity ultrasound at a total acoustic power of 0.11 ± 0.005 W and peak spatial intensity at the cannula tip of 49.7 mW/cm2. An additional 4 Sprague-Dawley rats (350–450 g) received UCED at 4 different and higher ultrasound intensities at the cannula tip ranging from 62.0 to 155.0 mW/cm2 for 30 minutes. The 3D infusion distribution was reconstructed using MATLAB analysis. Tissue damage and morphological changes to the brain were assessed using H & E. Results The application of ultrasound during infusion (UCED and UCED + MB) improved the volumetric distribution of EBD in the brain by a factor of 2.24 to 3.25 when there were no microbubbles in the infusate and by a factor of 1.16 to 1.70 when microbubbles were added to the infusate (p < 0.001). On gross and histological examination, no damage to the brain tissue was found for any acoustic exposure applied to the brain. Conclusions The TCA and ultrasound device show promise to improve the distribution of infused compounds during CED. The results suggest further studies are required to optimize infusion and acoustic parameters for small compounds and for larger molecular weight compounds that are representative of promising antitumor agents. In addition, safe levels of ultrasound exposure in chronic experiments must be determined for practical clinical evaluation of UCED. Extension of these experiments to larger animal models is warranted to demonstrate efficacy of this technique.

scholarly journals Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) Modulates TCD4+ and TCD8+ Cell Profile of Doxorubicin-Induced Immuno-Suppressed Rats

2019 ◽  
Vol 7 (22) ◽  
pp. 3774-3776
Author(s):  
Mustafa Ridwan Lubis ◽  
Reny Haryani ◽  
Safriana Safriana ◽  
Denny Satria
Keyword(s):  
Ethanolic Extract ◽  
Immune Functions ◽  
Sprague Dawley ◽  
Immunomodulatory Effects ◽  
Once Daily ◽  
Sprague Dawley Rats ◽  
Group 3 ◽  
Group 2 ◽  
Cell Profile ◽  
Group 1

AIM: To evaluate the immunomodulatory effects of ethanolic extract of herb pugun tanoh on TCD4 and TCD8 cells in Doxorubicin-induced rats. METHODS: Fifteen male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, DOX-treated rats (4.67 mg/kg BW body weight on day 1 and 4) and were administered normal saline 0.9% orally once daily for 7 consecutive days, Group 2, receiving Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) of dose 150 mg/kg BW orally, Group 3, receiving dose Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) 300 mg/kg BW orally. The rats of group 2-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1-4 to suppress immune functions. RESULTS: Treatment of 300 mg/kg BW of Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) succeeded in reducing side effect doxorubicin based on increasing the TCD4+ and TCD8+ blood level. CONCLUSION: Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) could increase the level of TCD4+ and TCD8+ in rats which induced by doxorubicin.

A Comparison of Arterial and Venous Flaps

1992 ◽  
Vol 17 (3) ◽  
pp. 359-364 ◽  
Author(s):  
S. P. CHOW ◽  
D. Z. CHEN ◽  
Y. D. GU
Keyword(s):  
Survival Rate ◽  
Elastic Properties ◽  
Perfusion Pressure ◽  
Skin Flap ◽  
Sprague Dawley ◽  
Venous Flaps ◽  
Sprague Dawley Rats ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The survival rate and elastic properties of the anterior abdominal skin flap in Sprague-Dawley rats were studied in three groups of animals. In group 1 where the flaps were supplied by a normal artery, arterial flaps (1A) had better survival rate and elastic properties than venous flaps (1B). In group 2, where the flaps were supplied by an artery with diminished perfusion pressure, the arterial flaps (2A) still had slightly better results than venous flaps (2B). However, in group 3 where the flaps were supplied by a vein, venous flaps (3B) had better results than arterial flaps (3A).

scholarly journals The Effect of Resveratrol on Surgery-Induced Epidural Fibrosis in Laminectomy Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Peifeng Sun ◽  
Bo Miao ◽  
Hongmei Xin ◽  
Jinzhu Zhao ◽  
Guofeng Xia ◽  
...  
Keyword(s):  
Treatment Group ◽  
Inflammatory Factors ◽  
Epidural Fibrosis ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Blinded Study ◽  
Group 3 ◽  
Group 2 ◽  
Double Blinded ◽  
Group 1

Epidural fibrosis (EF) is a common complication for the patients who underwent laminectomy. Recently, EF is thought to cause recurrent postoperative pain after laminectomy. Resveratrol has been shown to exert its anti-inflammatory, antifibrotic, and antiproliferative multifaceted properties. The object of this study was to investigate the effects of resveratrol on the prevention of postlaminectomy EF formation in laminectomy rats. A controlled double-blinded study was performed on 60 healthy adult Sprague-Dawley rats that underwent lumbar laminectomy at the L1-L2 levels. They were divided randomly into 3 groups (1, 2, and 3) of 20 rats each—group 1: resveratrol treatment group; group 2: resveratrol dilution saline treatment group; group 3: sham group (rats underwent laminectomy without treatment). All rats were killed 4 weeks after operation. The Rydell score, hydroxyproline content, vimentin cells density, fibroblasts density, and inflammatory factors expressional levels all suggested better results in resveratrol group than the other two groups. Resveratrol is able to inhibit fibroblasts proliferation, and TGF-β1 and IL-6 expressions and prevent epidural fibrosis in postlaminectomy rat.

scholarly journals Assessment of Nanosilver Hemocompatibility in Prehypertensive Salt-Induced Animal Model

2021 ◽  
Vol 2 (7) ◽  
pp. 567-573
Author(s):  
Ogechukwu K Uche ◽  
Esiri F Ohiambe ◽  
Fabian C Amechina
Keyword(s):  
Tap Water ◽  
Osmotic Fragility ◽  
Sprague Dawley ◽  
Group 4 ◽  
Sprague Dawley Rats ◽  
Normal Rat ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Aim: There are Conflicting reports on safety profile of nanoparticles on biological cells. This study evaluated the impact of nanosilver on hemocompatibility on salt-loaded rats. Materials and Methods: Sprague-Dawley rats [(inbred) (120-140 g)] randomly divided into of 4 groups, (n = 6) were studied. Group 1(control) received normal rat chow and tap water, Group 2 received rat chow containing 8% NaCl [(salt-loaded rats (SLRs)]. Group 3 received rat chow + Nanosilver Solution (NS) 0.18 mL 10 ppm/kg/day. Group 4 comprised SLRs + NS. After 6 weeks oral gavage treatments, measurements of Blood pressure (Bp) and Heart Rate (HR) were by pressure transducer via cannulation of left common carotid artery following anaesthesia with urethane. HR was computed by the number of arterial pulse per 60 seconds. 5 ml of blood for WBC, PLATELETS, RBC, PCV, HB, MCH, MCHC and MCV analyses using automated haematology analyser and Osmotic fragility reactivity with standard spectrophotometer at 540 nm wavelength. Results: Exposure of nanosilver to normotensive rats resulted in significantly lower RBC level compared with control, whereas RBC level in Salt-Loaded Co-Treated Nanosilver (SCNS) was comparable with the SLRs. The tenet was the same for HB, PCV, MCH and MCHC. Nanosilver induced leukopenia in normotensive compared with control and prevented WBC elevation in SCNS. Platelets significantly increased in Nanosilver-Treated Normotensive Rats (NTNRs) compared with control and decreased in SCNS. Osmotic burst resistance increased in NTNRs and decreased in cells from treated groups. Conclusion: Chronic exposure of nanosilver to salt loaded rats alters haematological parameters which may worsen circulatory function and activate risk factors of cardiovascular disorders.

Metalloendopeptidases EC 3.4.24.15/16 regulate bradykinin activity in the cerebral microvasculature

2003 ◽  
Vol 284 (6) ◽  
pp. H1942-H1948 ◽  
Author(s):  
M. Ursula Norman ◽  
Rebecca A. Lew ◽  
A. Ian Smith ◽  
Michael J. Hickey
Keyword(s):  
Specific Inhibitor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cerebral Microvasculature ◽  
Microvessel Permeability ◽  
The Brain ◽  
Cerebral Microvessel

Bradykinin is a vasoactive peptide that has been shown to increase the permeability of the cerebral microvasculature to blood-borne macromolecules. The two zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) degrade bradykinin in vitro and are highly expressed in the brain. However, the role that these enzymes play in bradykinin metabolism in vivo remains unclear. In the present study, we investigated the role of EP 24.15 and EP 24.16 in the regulation of bradykinin-induced alterations in microvascular permeability. Permeability of the cerebral microvasculature was assessed in anesthetized Sprague-Dawley rats by measuring the clearance of 70-kDa FITC dextran from the brain. Inhibition of EP 24.15 and EP 24.16 by the specific inhibitor N-[1-( R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr- p-aminobenzoate (JA-2) resulted in the potentiation of bradykinin-induced increases in cerebral microvessel permeability. The level of potentiation was comparable to that achieved by the inhibition of angiotensin-converting enzyme. These findings provide the first evidence of an in vivo role for EP 24.15/EP 24.16 in brain function, specifically in regulating alterations in microvessel permeability induced by exogenous bradykinin.

EFFECTS OF SEVERE HEMORRHAGE ON IN VIVO BRAIN AND SMALL INTESTINE MITOCHONDRIAL NADH AND MICROCIRCULATORY BLOOD FLOW

2008 ◽  
Vol 01 (02) ◽  
pp. 177-183 ◽  
Author(s):  
MIRA M. MANDELBAUM ◽  
EFRAT BARBIRO-MICHAELY ◽  
MICHAEL TOLMASOV ◽  
AVRAHAM MAYEVSKY
Keyword(s):  
Blood Flow ◽  
Small Intestine ◽  
Energy State ◽  
Critical Conditions ◽  
Tissue Blood Flow ◽  
Clinical Environment ◽  
Group 2 ◽  
The Brain ◽  
Group 1

Severe body stress induced by hypoxemia and hypotension may lead to total body energy state deterioration. The perfusion of the most vital organs is maintained at the expense of "less vital" organs. In the present study, we used a multi-site multi-parametric (MSMP) monitoring system for real-time evaluation of tissue blood flow (TBF) and mitochondrial NADH fluorescence of the brain and the small intestine following hemorrhage. In Group 1, uncontrolled hemorrhage, mean arterial pressure (MAP) was decreased to 40 mmHg within 2 minutes and shed blood was re-infused after 30 minutes. In Group 2, controlled hemorrhage, during the 30 minutes of hemorrhage, MAP was kept at 40 mmHg. During hemorrhage, in both groups, the intestinal TBF and NADH deteriorated, while the brain remained relatively well protected. In Group 1, all parameters partly recovered within the hemorrhage phase, while in Group 2, complete recovery occurred only after resuscitation. At the end of the experiment, both models showed a decrease in intestinal viability (TBF decreased, NADH increased), while the brain metabolic state in Group 2 declined slightly. Our unique multi-parametric monitoring device demonstrated that, under hemorrhage, the small intestine responded entirely differently from the brain. This may suggest the potential usefulness of the monitoring of less vital organs, as proxy organs, in critical conditions such as massive hemorrhage. The present study also highlights the importance of mitochondrial function monitoring in similar conditions in the clinical environment.

scholarly journals Preventive and therapeutic effects of relaxin on bisphosphonaterelated osteonecrosis of the jaw: an experimental study in rats

2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Tuba Develi ◽  
Sina Uckan ◽  
Burak Bayram ◽  
Kagan Deniz ◽  
Remzi Saban Erdem ◽  
...  
Keyword(s):  
Osteonecrosis Of The Jaw ◽  
Incidence Rates ◽  
Therapeutic Effects ◽  
Differentiation Process ◽  
Sprague Dawley ◽  
Group 4 ◽  
Sprague Dawley Rats ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits anti-fibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats’ mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ.KEYWORDSAnimal model; BRONJ; Relaxin.

Role of ATP-sensitive potassium channels in brain stem circulation during hypotension

1997 ◽  
Vol 273 (3) ◽  
pp. H1342-H1346 ◽  
Author(s):  
K. Toyoda ◽  
K. Fujii ◽  
S. Ibayashi ◽  
T. Kitazono ◽  
T. Nagao ◽  
...  
Keyword(s):  
Brain Stem ◽  
Basilar Artery ◽  
Katp Channels ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Sprague Dawley Rats ◽  
The Brain

The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.

Determination of rat brain buffering in vivo by 31P-NMR

1988 ◽  
Vol 64 (5) ◽  
pp. 1829-1836 ◽  
Author(s):  
S. Adler ◽  
V. Simplaceanu ◽  
C. Ho
Keyword(s):  
Rat Brain ◽  
Time Course ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Brain Ph ◽  
Acid Extrusion ◽  
The Brain ◽  
Full Activation

Buffering capacity of most tissues is composed of both rapid and slow phases, the latter presumably due to active acid extrusion. To examine the time course of brain buffering the brain pH of Sprague-Dawley rats was measured using 31P-nuclear magnetic resonance. The effect on brain pH of 30- or 58-min exposures to 20% CO2 followed by 30- or 38-min recovery periods, respectively, was studied. Brain pH reached its lowest value after a 15-min exposure to elevated CO2, thereafter slowly and steadily increasing. During recovery brain pH rose rapidly in the first 5 min exceeding control brain pH by 0.08 pH units. Brain pH fell during the next 30 min despite increases in blood pH and decreases in blood CO2 tension. Calculated intrinsic brain buffering rose steadily threefold during the last 40 min of CO2 exposure and during the final 30 min of recovery. These data show that in rat brain there is a temporally late buffering process, most likely active acid extrusion, requiring greater than 30 min for full activation and at least 30 min for discontinuation.

Role of neuronal nitric oxide in methamphetamine neurotoxicity and protection by nNOS inhibitor

2000 ◽  
Vol 72 (6) ◽  
pp. 1001-1006 ◽  
Author(s):  
D. Desaiah ◽  
S. L. N. Reddy ◽  
S. Z. Imam ◽  
S. F. Ali
Keyword(s):  
Nitric Oxide ◽  
Brain Regions ◽  
Selective Inhibitor ◽  
Sprague Dawley ◽  
Catecholaminergic System ◽  
Sprague Dawley Rats ◽  
Oxide Synthase ◽  
The Brain

Methamphetamine (METH) is a potent psychostimulant known to produce neurotoxicity. The dopaminergic pathway is particularly sensitive to METH. Recent studies showed that 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS), provided protection against METH neurotoxicity both in vitro and in vivo. The present studies were conducted to determine the nNOS activity in various regions of the brain of young adult male Sprague-Dawley rats treated with different doses of METH. Rats were injected ip with 5, 10, 20, and 40 mg/kg and 24 h after the rats were sacrificed and the brain regions (hippocampus, frontal cortex, and cerebellum) were quickly dissected. The cytosolic fractions were prepared, and the nNOS activity was determined using the 3H-citrulline assay. The results showed that nNOS activity was significantly increased in all three brain regions of rats treated with METH. The increase was dose dependent reaching a maximum of 40-100% over the control values. Rats treated with 7NI 30 min prior to METH injection provided protection against the toxicity and also showed a reduction of nNOS activity. The activation of nNOS is known to increase the synthesis of NO which is involved in the regulation of several neurotransmitter pathways including catecholaminergic system. Reducing the METH-induced production of NO by pretreatment with selective inhibitor of nNOS, 7-NI, provided protection against METH neurotoxicity.

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