Abstract WP256: Pretreatment of Rosuvastatin Ameliorates Early Brain Injury after Subarachnoid Hemorrhage through the Inhibition of Microglial Activation in Rats.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ken Uekawa ◽  
Yu Hasekawa ◽  
Mingjie Ma ◽  
Takashi Nakagawa ◽  
Tetsuji Katayama ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Brain Edema ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Early Brain Injury ◽  
Water Soluble ◽  
Vehicle Group ◽  
Protective Effects ◽  
Anti Inflammatory

BACKGROUND AND PURPOSE: We investigated the protective effects of pretreatment of oral-administered rosuvastatin, a water soluble HMG-CoA reductase inhibitor, on early brain injury (EBI) after subarachnoid hemorrhage (SAH). METHOD: Male Sprague-Dawley rats were operated on with endovascular perforation model and randomly divided into 4 groups: sham-operated, SAH+vehicle, SAH+1mg/kg, or 10mg/kg rosuvastatin. The animals in treatment groups were administered with daily oral rosuvastatin from 7 days before to 1 day after operation. All rats were evaluated regarding neurofunction, brain edema, and blood-brain barrier (BBB) disruption at 24 hours after SAH. Anti-inflammatory responses were also conducted using Western blot and immunohistochemistry at 24 hours after SAH. RESULTS: Compared with the vehicle group, rosuvastatin significantly improved the neurofunction score (modified Garcia score/ 22: 13.0±1.6 vs 17.0±1.0, P <0.05) , brain edema (brain water content: 79.11±0.15% vs 78.68±0.09%, P <0.05) , and BBB disruption (IgG extravasation); data are showed as a mean±SEM. Rosuvastatin reduced number of activated microglial cells , activation of nuclear factor-kappa B(NF-kB), and expression of tumor necrosis factor-alpha (TNF-α) , which were considered as markers of inflammatory response from microglia, and downregulated the expression of neuronal cyclooxygenase-2 (COX-2) and endothelial matrix metalloproteinase-9 (MMP-9). CONCLUSION: The current study showed that pretreatment of rosuvastatin induced anti-inflammatory processes through inhibition of microglial activation and thereby attenuated early brain injury. Rosuvastatin seems to be a promising agent for treatment of SAH.

Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

2014 ◽  
Vol 121 (1) ◽  
pp. 42-54 ◽  
Author(s):  
Xiang-Sheng Zhang ◽  
Xin Zhang ◽  
Meng-Liang Zhou ◽  
Xiao-Ming Zhou ◽  
Ning Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Oral Administration ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Early Brain Injury ◽  
Antioxidant Property ◽  
Neural Cell ◽  
Intracerebroventricular Injection

Object Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property. Methods Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation. Results It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH. Conclusions These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

scholarly journals SOCS1/JAK2/STAT3 axis regulates early brain injury induced by subarachnoid hemorrhage via inflammatory responses

2021 ◽  
Vol 16 (12) ◽  
pp. 2453
Author(s):  
Yong-Fei Dong ◽  
Chao-Shi Niu ◽  
Yang Wang ◽  
Xiang-Qian Kong ◽  
Fei Wu ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Early Brain Injury

Abstract 2611: Inhibition Of Rho-kinase By Hydroxyfasudil Attenuates Early Brain Injury After Subarachnoid Hemorrhage In Rats

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mutsumi Fujii ◽  
Kamil Duris ◽  
Orhan Altay ◽  
Yoshiteru Soejima ◽  
Prativa Sherchan ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Edema ◽  
Rho Kinase ◽  
Early Brain Injury ◽  
Vehicle Group ◽  
Brain Water Content ◽  
Single Treatment ◽  
Ipsilateral Hemisphere ◽  
Neurological Score ◽  
Brain Water

Background: Early brain injury comprising of blood-brain barrier (BBB) disruption and brain edema is an important part of subarachnoid hemorrhage (SAH) pathophysiology. Although several reports have shown that inhibition of Rho-kinase (ROCK) plays an important role in suppressing barrier permeability, the effect of ROCK on the BBB in SAH is not well understood. Therefore, we assessed the hypothesis that (A) ROCK inhibitors, hydroxyfasudil (HF) and Y27632 attenuate early brain injury after SAH, and (B) HF decreases brain edema via preservation of the BBB. Methods: Adult male rats were randomly assigned to five groups; sham-operated, SAH with saline, SAH with HF (10mg/kg, i.p.) treatment at 0.5 hrs, SAH with HF (10mg/kg, i.p.) treatment at 0.5 and 6 hrs each , and SAH with Y27632 (10mg/kg, i.p.) treatment at 0.5 hrs. The endovascular perforation method was used to produce SAH. Neurological scores were evaluated before sacrifice at 24 and 72 hours after injury. Brain water content, Evans blue dye extravasation assay, Rho-kinase activity assay, and Western blotting analyses were performed. Results: Among 175 surgeries performed, 53 animals were excluded. Of those excluded, 26 died from severe SAH and 27 had only mild SAH. There were no differences between the SAH with saline group (Vehicle group), SAH with HF group, and SAH with Y27632 group in SAH grading and mortality. HF but not Y27632 significantly improved neurological outcomes. Both groups significantly attenuated brain water content (BWC) in the ipsilateral hemisphere compared with the Vehicle group at 24 hrs after SAH for single treatment. The BWC of the HF group was also significantly lower than that of the Vehicle group in the contralateral hemisphere and cerebellum. There was no difference in neurological score between the Vehicle and HF group with two treatments, however, HF significantly ameliorated BWC in the ipsilateral hemisphere compared with vehicle at 24 hrs after SAH. There was no difference in neurological score and BWC between the Vehicle and HF groups with single treatment at 72 hrs after SAH. Evans blue extravasation in the ipsilateral hemisphere in the Vehicle group was significantly higher than in the HF group for single treatment at 24 hours after SAH. Supernatants of the ipsilateral hemisphere of single treatment groups sacrificed at 24 hours showed significantly higher ROCK activity in the Vehicle group than the sham group, and the HF group showed significantly lower activity than the Vehicle group. As the tight junction (TJ) is one of the components of the endothelial junctional complex in the BBB, we evaluated TJ proteins, occludin and Zona occludens-1 (ZO-1) in Western blotting analyses. Occludin and ZO-1 levels were significantly lower in the Vehicle group than the HF group. Conclusion: The ROCK inhibitor, HF, attenuates early brain injury by decreasing brain edema after SAH via protection of tight junction proteins.

scholarly journals Sodium/Hydrogen Exchanger 1 Participates in Early Brain Injury after Subarachnoid Hemorrhage both in vivo and in vitro via Promoting Neuronal Apoptosis

2019 ◽  
Vol 28 (8) ◽  
pp. 985-1001 ◽  
Author(s):  
Huangcheng Song ◽  
Shuai Yuan ◽  
Zhuwei Zhang ◽  
Juyi Zhang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Brain Edema ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger

Sodium/hydrogen exchanger 1 (NHE1) plays an essential role in maintaining intracellular pH (pHi) homeostasis in the central nervous system (CNS) under physiological conditions, and it is also associated with neuronal death and intracellular Na+ and Ca2+ overload induced by cerebral ischemia. However, its roles and underlying mechanisms in early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) have not been fully explored. In this research, a SAH model in adult male rat was established through injecting autologous arterial blood into prechiasmatic cistern. Meanwhile, primary cultured cortical neurons of rat treated with 5 μM oxygen hemoglobin (OxyHb) for 24 h were applied to mimic SAH in vitro. We find that the protein levels of NHE1 are significantly increased in brain tissues of rats after SAH. Downregulation of NHE1 by HOE642 (a specific chemical inhibitor of NHE1) and genetic-knockdown can effectively alleviate behavioral and cognitive dysfunction, brain edema, blood-brain barrier (BBB) injury, inflammatory reactions, oxidative stress, neurondegeneration, and neuronal apoptosis, all of which are involved in EBI following SAH. However, upregulation of NHE1 by genetic-overexpression can produce opposite effects. Additionally, inhibiting NHE1 significantly attenuates OxyHb-induced neuronal apoptosis in vitro and reduces interaction of NHE1 and CHP1 both in vivo and in vitro. Collectively, we can conclude that NHE1 participates in EBI induced by SAH through mediating inflammation, oxidative stress, behavioral and cognitive dysfunction, BBB injury, brain edema, and promoting neuronal degeneration and apoptosis.

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