Dodecafluoropentane Emulsion (DDFPe) Decreases Stroke Size and Improves Neurological Scores in a Permanent Occlusion Rat Stroke Model

Background: Dodecafluoropentane emulsion (DDFPe), given IV one hour after stroke, has been shown to greatly reduce the percent stroke volume (%SV) in rabbits. With repeated doses its effect continued for 24 hours. Purpose: Test DDFPe as neuroprotective agent in permanent occlusion rat stroke models in Sprague Dawley (SD) and Spontaneously Hypertensive Rats (SHR) measuring both %SV and neurological assessment scores (NAS). Methods: The male rats received either saline (control), or one or four doses (1x or 4x) of DDFPe (0.6ml/kg IV) one hour post stroke. Treatment groups were SD (n=26) (control, 1x and 4x; n=12, 7 and 7) and SHR (n=14) (control, 1x and 4x; n=7, 3 and 4). The 4x doses were given at 1.5 hour intervals. At six hours post stroke, the rats received a NAS using standard tests for balance, reflexes, and motor performance. Then rats were euthanized and brains removed for TTC evaluation of %SV. Results: For %SV analysis strain differences were not significant therefore strains were combined. DDFPe significantly decreased %SV in 1x and 4xDDFPe groups compared to control groups (2.59±1.81 and 0.98±0.88 vs. 9.24±6.06, p≤0.001 each; p≤0.0001 for the overall test for treatment effect). The 1x versus 4xDDFPe groups were not significantly different (p=0.40). In NAS analysis both strains showed significant improvement with 4xDDFPe therapy vs. controls, (SD: 5.00+2.45 vs. 9.36+3.56, p=0.01; SHR: 7.75+4.43 vs. 12.14+3.08, p=0.05). Differences between the 1x DDFPe group and controls were not significant (SD: 8.43+3.69; SHR: 9. 33+3.51). Conclusion: DDFPe treatment provides significant neuroprotection when assessed six hours post stroke.

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Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.4.f655 ◽

1986 ◽

Vol 251 (4) ◽

pp. F655-F661 ◽

Cited By ~ 3

Author(s):

M. A. Rudd ◽

R. S. Grippo ◽

W. J. Arendshorst

Keyword(s):

Sodium Excretion ◽

Renal Denervation ◽

Strain Differences ◽

Urine Flow ◽

Sprague Dawley ◽

Renal Vasculature ◽

Renal Nerve ◽

Water Excretion ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.

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A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels

Translational Stroke Research ◽

10.1007/s12975-020-00848-3 ◽

2020 ◽

Author(s):

Yi Wang ◽

Jae H. Choi ◽

Mohammed A. Almekhlafi ◽

Ulf Ziemann ◽

Sven Poli

Keyword(s):

Ischemic Stroke ◽

Artery Occlusion ◽

Brain Cooling ◽

Sprague Dawley ◽

Total Blood ◽

Pilot Studies ◽

Stroke Treatment ◽

Stroke Models ◽

Cold Infusion ◽

Cerebral Artery Occlusion

Abstract Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat’s total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.

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Post-stroke treatment with K-134, a phosphodiesterase 3 inhibitor, improves stroke outcomes in the stroke-prone spontaneously hypertensive rat model - a comparative evaluation of antiplatelet drugs

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2021.12.001 ◽

2021 ◽

Author(s):

Hideo Yoshida ◽

Shinsuke Itoh ◽

Farhana Ferdousi ◽

Hiroko Isoda

Keyword(s):

Rat Model ◽

Comparative Evaluation ◽

Spontaneously Hypertensive Rat ◽

Antiplatelet Drugs ◽

Stroke Outcomes ◽

Stroke Treatment ◽

Spontaneously Hypertensive ◽

Post Stroke ◽

Phosphodiesterase 3 ◽

Spontaneously Hypertensive Rat Model

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In vivo basal and amphetamine-induced striatal dopamine and metabolite levels are similar in the spontaneously hypertensive, Wistar–Kyoto and Sprague–Dawley male rats

Physiology & Behavior ◽

10.1016/s0031-9384(03)00214-2 ◽

2003 ◽

Vol 80 (1) ◽

pp. 109-114 ◽

Cited By ~ 12

Author(s):

Sherry A Ferguson ◽

Bobby J Gough ◽

Amy M Cada

Keyword(s):

Striatal Dopamine ◽

Male Rats ◽

Sprague Dawley ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

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Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats

Fundamental and Clinical Pharmacology ◽

10.1111/j.1472-8206.1999.tb00006.x ◽

1999 ◽

Vol 13 (4) ◽

pp. 475-483 ◽

Cited By ~ 5

Author(s):

Fumie Yabuuchi ◽

Masaya Takahashi ◽

Kosuke Aritake ◽

Mineko Fujimoto ◽

Hajime Ito ◽

...

Keyword(s):

Spontaneously Hypertensive Rats ◽

Brain Oedema ◽

Hypertensive Rats ◽

Learning Deficits ◽

Stroke Treatment ◽

Spontaneously Hypertensive ◽

Post Stroke

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Systemic hemodynamic effects of microspheres in conscious rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1977.233.5.h617 ◽

1977 ◽

Vol 233 (5) ◽

pp. H617-H621 ◽

Cited By ~ 3

Author(s):

M. Tsuchiya ◽

G. M. Walsh ◽

E. D. Frohlich

Keyword(s):

Venous Blood ◽

Peripheral Resistance ◽

Male Rats ◽

Blood Oxygen ◽

Hemodynamic Effects ◽

Sprague Dawley ◽

Systemic Hemodynamic ◽

Spontaneously Hypertensive ◽

Content Difference ◽

Wistar Kyoto

The effect of increasing quantities of carbonized microspheres (15 +/- 5 micrometer diam) on systemic hemodynamics was evaluated in 21 Sprague-Dawley, 6 normotensive Wistar-Kyoto (WKY), and 8 spontaneously hypertensive (SHR) male rats. Total cumulative injections of more than 100,000 microspheres produced significant systemic hemodynamic alterations manifested by decreased oxygen consumption, cardiac output, and mean arterial pressure; and by increased heart rate, total peripheral resistance, and arterial-venous blood oxygen content difference. There were no hemodynamic alterations characteristic of any rat species, and reproducibility of three separate injections of 20,000 microspheres in each rat was excellent.

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Parathyroidectomy significantly decreases hypertension in spontaneously hypertensive and deoxycorticosterone plus saline treated rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y82-033 ◽

1982 ◽

Vol 60 (2) ◽

pp. 208-212 ◽

Cited By ~ 13

Author(s):

Alexis Gairard ◽

Alain Berthelot ◽

René Schleiffer ◽

Fanny Pernot

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Systolic Blood Pressure ◽

Normal Serum ◽

Male Rats ◽

Shr Rats ◽

Sprague Dawley ◽

Spontaneously Hypertensive ◽

Sprague Dawley Rats ◽

Normal Serum Calcium

In male Sprague–Dawley rats, hypertensive development was diminished for 10 weeks when parathyroidectomy (PTX) was performed 1 week before deoxycorticosterone plus saline (DOCA + NaCl) treatment. In young spontaneously hypertensive male rats (SHR, Okamoto strain) parathyroidectomy performed after weaning lessened hypertensive levels and lowered heart rate for 24 weeks. When mineralocorticoid or genetic hypertension was established, parathyroidectomy did not significantly change blood pressure levels. High dietary calcium in PTX–SHR rats reestablished normal serum calcium but not systolic blood pressure to the level of sham SHR. From our present and previously reported results, it appears that the parathyroid gland is necessary for the total development of hypertension in both models.

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Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/1028909 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Feng Niu ◽

Cuiting Wang ◽

Hequan Zhong ◽

Ningna Ren ◽

Xiaokun Wang ◽

...

Keyword(s):

Cerebral Palsy ◽

Memory Function ◽

Male Rats ◽

Balance Function ◽

Behavioral Tests ◽

Sprague Dawley ◽

Cerebral Disease ◽

Mortality And Morbidity ◽

Permanent Occlusion ◽

Anaerobic Environment

Cerebral palsy (CP) is a severe cerebral disease with high mortality and morbidity, which leads to great challenges for the suffering children and their families. Hence, the need for the efficacious and safe treatments is urgent. As a physical therapy arising from traditional Chinese medicine (TCM), Tuina has shown multiple effects on various diseases, including cerebral palsy. Nevertheless, the detailed mechanisms of Tuina on CP remain unknown, which impedes its further clinical application. Herein, we explored the effects of Tuina on CP and its potential mechanisms. Thirty Sprague Dawley (SD) male rats were randomly divided into sham, model, and Tuina groups (model + Tuina). CP rat model was established by hypoxia-ischemia via permanent occlusion of left common carotid artery and hypoxia for 2.5 hours caused by anaerobic environment, which was subsequently followed by onset of Tuina treatment from postnatal day 7 (P7) to P49. After completion of Tuina treatment, the behavioral tests showed that Tuina treatment not only improved the retarded body weight and impaired motor balance function, but also ameliorated weakened learning and memory function of CP rats. Moreover, immunohistochemistry and western blot also revealed a reduced expression of NLRP3 inflammasome and corresponding pyroptosis-related molecules induced by NLRP3 in CP rats after Tuina treatment. Therefore, our study indicated that Tuina treatment may improve impaired neurocognitive function of CP rats, which was possibly realised via inhibiting NLRP3-induced pyroptosis.

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Abstract TP113: Delayed (21 Days) Post Stroke Treatment With RPh201, A Botany-Derived Compound, Improves Neurological Functional Recovery in a Rat Model of Embolic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp113 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Chunyang Wang ◽

Michael Chopp ◽

Rui Huang ◽

Yi Zhang ◽

William Golembieski ◽

...

Keyword(s):

Functional Recovery ◽

Infarct Volume ◽

Experimental Models ◽

Stroke Recovery ◽

Female Rats ◽

Male Rats ◽

Acute Stroke Care ◽

Stroke Treatment ◽

Post Stroke ◽

Male And Female Rats

Introduction: Despite the recent advances in the acute stroke care, treatment options for long-term disability are limited. RPh201 is a botany-derived bioactive compound that has been shown to exert beneficial effects in various experimental models of neural injury. However, the effect of RPh201 on stroke recovery has not been investigated. The present study evaluated the effect of RPh201 on functional recovery after stroke. Methods: Young adult Wistar rats subjected to embolic middle cerebral artery occlusion (MCAO) were randomized into the following experimental groups stratified by sex (n=20/group): 1) RPh201 treatment, and 2) vehicle (cottonseed oil). RPh201 (20 μl) or vehicle were subcutaneously administered twice a week for 16 consecutive weeks starting at 21 days after MCAO. An array of behavioral tests were performed during 120 days after treatment initiation. Results: Male, but not female, ischemic rats treated with RPh201 exhibited significant (p<0.05) improvement of neurological function measured by adhesive removal test, foot-fault test, and modified neurological severity score at 90 and 120 days after initiation of treatment. Immunohistochemistry analysis showed that RPh201 treatment robustly increased neurofilament heavy chain positive axons and myelin basic protein densities in the peri-infarct area by 61% and 31% in the male rats, respectively, when compared to the vehicle treatment, which were further confirmed by Western blot analysis. The RPh201 treatment did not reduce infarct volume in both male and female rats. Conclusions: Our data demonstrated that RPh201 has a therapeutic effect on improvement of functional recovery in male ischemic rats even when the treatment was initiated 21 days post stroke. Enhanced axonal and myelination densities by RPh201 in ischemic brain may contribute to improved stroke recovery.

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