Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke

10.1038/72256 ◽  
2000 ◽  
Vol 6 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Geoffrey T. Manley ◽  
Miki Fujimura ◽  
Tonghui Ma ◽  
Nobuo Noshita ◽  
Ferda Filiz ◽  
...  
Author(s):  
Takafumi Nakano ◽  
Chisa Nishigami ◽  
Keiichi Irie ◽  
Yutaka Shigemori ◽  
Kazunori Sano ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e84602 ◽  
Author(s):  
Zhijie He ◽  
Xiaolou Wang ◽  
Yi Wu ◽  
Jie Jia ◽  
Yongshan Hu ◽  
...  

2018 ◽  
Vol 17 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Bogdan Catalin ◽  
Otilia-Constantina Rogoveanu ◽  
Ionica Pirici ◽  
Tudor Adrian Balseanu ◽  
Adina Stan ◽  
...  

Background: Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. Objective: New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. Methods: Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. Results: We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronalsurvival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. Conclusion: Our data show that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hannah J Irvine ◽  
Thomas W Battey ◽  
Ann-Christin Ostwaldt ◽  
Bruce C Campbell ◽  
Stephen M Davis ◽  
...  

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.


2020 ◽  
Vol 319 ◽  
pp. 160-167 ◽  
Author(s):  
Yizhou Zhong ◽  
Boxuan Liang ◽  
Manjiang Hu ◽  
Jun Liu ◽  
Li Lin ◽  
...  

2014 ◽  
Vol 63 ◽  
pp. 222-228 ◽  
Author(s):  
Kakulavarapu V. Rama Rao ◽  
A.S. Verkman ◽  
Kevin M. Curtis ◽  
Michael D. Norenberg

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Hubin Duan ◽  
Chunyan Hao ◽  
Shengqiang Duan ◽  
suping Wang ◽  
Weiqing Gao ◽  
...  

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