Abstract WP106: Attenuation of Stroke Damage by Angiotensin II Type 2 Receptor Stimulation via Peroxisome Proliferator-Activated Receptor-gamma Activation

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Bao-Shuai Shan ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Hui-Yu Bai ◽  
Masayoshi Kukida ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Peroxisome Proliferator ◽  
Ischemic Brain Injury ◽  
Receptor Stimulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ischemic Brain ◽  
Ppar Γ ◽  
Mca Occlusion

Introduction and hypothesis: Brain renin–angiotensin system plays a role in ischemic brain damage after stroke. It is known that stimulation of angiotensin II type 2 (AT 2 ) receptor has a protective role in ischemic brain injury. We demonstrated that AT 2 receptor stimulation by compound 21 (C21), direct AT 2 receptor agonist, inhibited vascular intimal proliferation with activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ). Agents with PPAR-γ agonistic effect have been demonstrated to be neuroprotective in brain ischemia. However, whether direct AT 2 receptor stimulation has a protective effect on ischemic brain injury via PPAR-γ activation is still unknown. Thus, we investigated the beneficial effect of C21 on ischemic brain damage by AT 2 receptor stimulation via PPAR-γ activation. Methods: Eight-week-old male C57BL/6J and human renin and human angiotensinogen double-transgenic (hRN/hANG-Tg) mice were subjected to middle cerebral artery (MCA) occlusion. Before MCA occlusion, they were administered C21 with or without GW9662, a PPAR-γ antagonist, for 2 weeks. Ischemic size, inflammation and oxidative stress were assessed 24 hours after MCA occlusion. Cerebral blood flow was measured in the core and periphery of the MCA territory before, immediately after, 1 hour and 24 hours after MCA occlusion. Results: Administration of C21 with or without GW9662 had no significant effect on blood pressure. Ischemic brain area at 24 hours after MCA occlusion was significantly enlarged in hRN/hANG-Tg mice, compared with C57BL/6J mice. Treatment with C21 decreased the ischemic area compared with the no-treatment group, with an increase in cerebral blood flow, both in C57BL/6J and hRN/hANG-Tg mice. Co-administration of GW9662 partially attenuated the protective effect of C21 on ischemic size, via an increment in the expression of inflammatory cytokines and superoxide production, although GW9662 treatment alone had no significant effect on ischemic size. Conclusions: These results suggest that direct AT 2 receptor stimulation has a beneficial effect on stroke partly due to activation of PPAR-γ.

Abstract WP113: Administration of Direct Angiotensin II Type-2 Receptor Agonist, Compound 21, Even After Stroke Prevents Ischemic Brain Damage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Masaki Mogi ◽  
Li-Juan Min ◽  
Fei Jing ◽  
Kana Tsukuda ◽  
Kousei Ohshima ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Damage ◽  
Receptor Agonist ◽  
Receptor Stimulation ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Compound 21 ◽  
Deficient Mice

Objectives: Previous our studies showed that angiotensin II type-2 (AT 2 ) receptor stimulation protects neurons after brain ischemic damage using AT 2 receptor-deficient mice. Recently, Compound 21 (C21) is available to use as a direct AT 2 receptor agonist. We reported that administration of C21 induces vascular dilatation via bradykinin-nitric oxide pathway and maintains cerebral blood flow, resulting in prevention of cognitive impairment. These results inspired us the possibility that administration of C21 could protect ischemic brain damage; therefore, we assessed the effect of C21 on stroke expansion by not only pre-treatment, but also a treatment immediately after stroke. Methods: 10 week-old wild-type male C57BL6 mice were subjected to the middle cerebral artery occlusion (MCAO) by electrocoagulation using a subtemporal approach. Ischemic area after stroke was evaluated by time-course analysis by magnetic resonance imaging (MRI) of the brain. C21 was administrated to mice 2 weeks before MCAO or immediately after MCAO treatment by intraperitoneal injection. Cerebral blood flow was evaluated by using 2D-laser speckle blood flow imaging system. Results: No significant remarkable change was observed in blood pressure in mice with or without C21 treatment. Pretreatment of C21 prevented ischemic brain damage 1 day after MCAO. In contrast, such preventive effect by C21 was not observed in AT 2 receptor-deficient mice. On the other hand, C21 treatment immediately after MCAO did not reduce ischemic area 1 day after MCAO, but remarkably reduced this 3 days after MCAO. Treatment with C21 prevented the reduced cerebral blood flow after MCAO. Conclusions: These findings indicate that AT 2 receptor stimulation by C21 prevents ischemic brain damage at least in part via maintaining cerebral blood flow even after stroke. Therefore, administration of C21 could work as a new therapeutical option in patients with stroke even in acute phase.

Cerebral Circulation and Cerebral Blood Flow

2019 ◽  
pp. 79-85
Author(s):  
Arnoley S. Abcejo ◽  
Jeffrey J. Pasternak
Keyword(s):  
Blood Flow ◽  
Cardiac Arrest ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Neurologic Outcomes ◽  
The Us ◽  
Hospital Cardiac Arrest ◽  
Premonitory Symptoms

Cardiac arrest occurs suddenly, often without premonitory symptoms. Consciousness is lost within seconds to minutes because of insufficient cerebral blood flow in the midst of complete hemodynamic collapse. Anoxic-ischemic brain injury is most commonly caused by cardiac arrest, which is frequently lethal; of the US patients with out-of-hospital cardiac arrest treated by emergency medical services, almost 90% die. Among the patients who survive to hospital admission, inpatient mortality may be decreasing, but a substantial number of those survivors have poor neurologic outcomes from anoxic-ischemic brain injury.

Role of peroxisome proliferator–activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus

2018 ◽  
Vol 37 (11) ◽  
pp. 1187-1198 ◽  
Author(s):  
A Tabassum ◽  
T Mahboob
Keyword(s):  
Oxidative Stress ◽  
Renal Damage ◽  
Peroxisome Proliferator ◽  
Advanced Glycation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Glycation End Products ◽  
End Products

The present study focused on the role of peroxisome proliferator–activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i.p. 35 mg/kg); group 5: T2DM rats treated with RSG (3 mg/kg orally for 7 days). Serum levels of AGEs and visfatin, renal damage, and oxidative stress were analyzed. Results showed that HFD-induced obesity and T2DM caused an elevated blood glucose, serum AGEs, visfatin, insulin, urea, creatinine, and tissue malondialdehyde, whereas a decreased catalase and superoxide dismutase activity were observed. The PPAR-γ activation via agonist restored these changes. Our findings suggest that AGEs and visfatin possess an important role in the progression of renal oxidative stress, which can be reduced by the PPAR-γ agonist that impede deleterious effects of HFD and HFD-induced T2DM on renal damage.

Temporal profiles of cerebral blood flow in neonatal mice with hypoxic–ischemic brain injury

2011 ◽  
Vol 71 ◽  
pp. e403
Author(s):  
Makiko Ohshima ◽  
Masahiro Tsuji ◽  
Yukiko Kasahara ◽  
Akihiko Taguchi ◽  
Tomoaki Ikeda
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Neonatal Mice ◽  
Hypoxic Ischemic Brain Injury ◽  
Temporal Profiles

scholarly journals Increased Susceptibility to Ischemic Brain Injury in Cyclooxygenase-1–Deficient Mice

2001 ◽  
Vol 21 (12) ◽  
pp. 1436-1441 ◽  
Author(s):  
Costantino Iadecola ◽  
Koreaki Sugimoto ◽  
Kiyoshi Niwa ◽  
Ken Kazama ◽  
M. Elizabeth Ross
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Cyclooxygenase 1 ◽  
Cox 1 ◽  
Increased Susceptibility

Cyclooxygenase-1 (COX-1), a rate-limiting enzyme in the synthesis of prostanoids, is involved in selected vasodilatatory responses of the cerebral circulation. Cyclooxygenase-1–null mice were used to determine whether COX-1 influences cerebral ischemic damage. The middle cerebral artery was occluded in COX-1 −/− and +/+ mice (n = 9/group), and lesion volume was determined in thionin-stained sections 24 or 96 hours later. Middle cerebral artery occlusion produced larger infarcts in COX-1 −/− mice, both at 24 (35 ± 17%; P < 0.05) and 96 hours (41 ± 16%; P < 0.05) after ischemia. The enlargement was not due to increased susceptibility to glutamate excitotoxicity, because microinjection of N-methl- d -asparatate or kainate in the parietal cortex produced comparable lesions in COX-1 +/+ and −/− mice ( P > 0.05; n = 8/group). To examine the contribution of hemodynamic factors to the enlargement of the infarct, cerebral blood flow was monitored by laser-Doppler flowmetry in the ischemic territory (n = 6/group). Although the reduction in cerebral blood flow was comparable in the ischemic core ( P > 0.05), at the periphery of the ischemic territory the reduction was greater in COX-1 −/− mice (−58 ± 4%) than in COX-1 +/+ mice (−34 ± 5%; P < 0.05). It is concluded that mice lacking COX-1 are more susceptible to focal cerebral ischemia, an effect that can be attributed to a more severe cerebral blood flow reduction in vulnerable regions at the periphery of the ischemic territory. Thus, the vascular effects of COX-1 may contribute to maintain cerebral blood flow in the postischemic brain and, as such, play a protective role in ischemic brain injury.

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