GABAergic contribution to rat bladder hyperactivity after middle cerebral artery occlusion

2000 ◽  
Vol 279 (4) ◽  
pp. R1230-R1238 ◽  
Author(s):  
Sayoko Kanie ◽  
Osamu Yokoyama ◽  
Kazuto Komatsu ◽  
Koichi Kodama ◽  
Satoshi Yotsuyanagi ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Receptor Agonist ◽  
Bladder Capacity ◽  
Artery Occlusion ◽  
Female Rats ◽  
Left Middle Cerebral Artery ◽  
Urethral Pressure ◽  
Cerebral Artery Occlusion

To evaluate the influences of γ-aminobutyric acid (GABA) mechanisms on bladder hyperactivity after left middle cerebral artery occlusion, cystometric recordings were obtained from unanesthetized female rats. Intracerebroventricular administration of both muscimol (GABAA receptor agonist; 0.1–10 nmol) and baclofen (GABAB receptor agonist; 0.1–3 nmol) produced dose-dependent inhibitions of micturition with increases in bladder capacity (BC). The effects of high doses (1–10 nmol) were similar in sham-operated (SO) and cerebral-infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABAA receptor antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first decreased and subsequently increased. An increase in urethral pressure was observed after administration of bicuculline (3 nmol) but not with either muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen-treated rats were not significantly different from those of vehicle-treated rats. These results suggest that GABAergic mechanisms inhibit the micturition reflex at the supraspinal level but that this can change as a result of CI.

scholarly journals Neuroprotective Efficacy of Repinotan HCl, a 5-HT1A Receptor Agonist, in Animal Models of Stroke and Traumatic Brain Injury

2005 ◽  
Vol 25 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Frank Mauler ◽  
Ervin Horváth
Keyword(s):  
Animal Models ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Receptor Agonist ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Occlusion Model ◽  
Neuroprotective Efficacy ◽  
Cerebral Artery Occlusion

Repinotan is a highly potent 5-HT1A receptor agonist with strong neuroprotective efficacy in animal models of middle cerebral artery occlusion and traumatic brain injury. In this study, we characterized the time window for neuroprotective effects of repinotan in animal models. In the permanent middle cerebral artery occlusion model, repinotan showed neuroprotective efficacy when administered as a triple bolus injection (0.3–100 μg/kg) or an intravenous infusion (0.3–100 μg/kg per hour). A 73% reduction in infarct volume was observed with a 3 μg/kg intravenous bolus, and a 65% reduction was observed with a 3 and 10 μg/kg per hour intravenous infusion. When delayed until 5 hours after occlusion, repinotan (10 μg/kg per hour) reduced infarct volume by 43%. In the transient middle cerebral artery occlusion model, repinotan (10 μg/kg per hour) administered immediately after occlusion reduced infarct volume by 97%, and a delay to 5 hours reduced infarct volume by 81%. In the acute subdural hematoma model, repinotan (3 and 10 μg/kg per hour) reduced infarct volume by 65%. In this model, repinotan (3 μg/kg per hour) administered 5 hours after occlusion reduced infarct volume by 54%. The favorable neuroprotective efficacy, broad dose–response curve, and prolonged therapeutic window observed in all models strongly suggest that repinotan is a promising candidate for treating acute ischemic stroke in humans.

scholarly journals Bryostatin extends tPA time window to 6 h following middle cerebral artery occlusion in aged female rats

2015 ◽  
Vol 764 ◽  
pp. 404-412 ◽  
Author(s):  
Zhenjun Tan ◽  
Brandon P. Lucke-Wold ◽  
Aric F. Logsdon ◽  
Ryan C. Turner ◽  
Cong Tan ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Time Window ◽  
Artery Occlusion ◽  
Female Rats ◽  
Cerebral Artery Occlusion

scholarly journals Worsened Outcome from Middle Cerebral Artery Occlusion in Aged Rats Receiving 17β-Estradiol

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3386-3393 ◽  
Author(s):  
Rachel L. Leon ◽  
Xinlan Li ◽  
Jason D. Huber ◽  
Charles L. Rosen
Keyword(s):  
Young Adult ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Female Rats ◽  
Aged Rats ◽  
Adult Rats ◽  
17Β Estradiol ◽  
Cerebral Artery Occlusion

Although estrogens are neuroprotective in young adult animal models of stroke, clinical trials demonstrate that estrogens increase the incidence and severity of stroke in aged women. We have previously shown that experimental stroke pathophysiology differs between young adult and aged rats. The aim of this study was to determine the effects of 17β-estradiol after middle cerebral artery occlusion and reperfusion in young adult and aged female rats. Focal embolic stroke was performed by middle cerebral artery occlusion with fibrin clot followed by reperfusion with iv human recombinant tissue plasminogen activator. Histological and functional outcomes were measured at 24 h after middle cerebral artery occlusion with fibrin clot. Aged rats treated with 17β-estradiol had significantly increased infarct volumes compared with placebo-treated aged rats. Young adult rats treated with 17β-estradiol had significantly decreased infarct volumes and improved functional outcome compared with ovariectomized young adult rats. Our results suggest that 17β-estradiol may act in an age-dependent manner in the postischemic rat brain. In young adult rats, it is neuroprotective; chronic treatment with 17β-estradiol during aging leads to worsened ischemic brain injury in aged female rats.

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