Dual-energy X-ray absorptiometry for detecting neurogenic pulmonary edema in a mouse model of subarachnoid hemorrhage

Tatsushi Mutoh , Hiroaki Aono , Yushi Mutoh , Tatsuya Ishikawa

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (6) : 1146 -1151.

PDF
Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (6) : 1146 -1151. DOI: 10.1002/ame2.70019
TECHNICAL NOTE

Dual-energy X-ray absorptiometry for detecting neurogenic pulmonary edema in a mouse model of subarachnoid hemorrhage

Author information +
History +
PDF

Abstract

Murine subarachnoid hemorrhage (SAH) induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH. However, identifying mice with comorbid acute neurogenic pulmonary edema (NPE), a life-threatening systemic consequence often induced by SAH, in this model is difficult without histopathological investigations. Herein, we present an imaging procedure involving dual-energy X-ray absorptiometry (DXA) to identify NPE in a murine model of SAH. We quantified the lung lean mass (LM) and compared the relationship between micro-computed tomography (CT) evidence of Hounsfield unit (HU) values and histopathological findings of PE. Of the 85 mice with successful induction of SAH by filament perforation, 16 (19%) had NPE, as verified by postmortem histology. The DXA-LM values correlate well with CT-HU levels (r = 0.63, p < 0.0001). Regarding the relationship between LM and HU in mice with post-SAH NPE, the LM was positively associated with HU values (r2 = 0.43; p = 0.0056). A receiver operating characteristics curve of LM revealed a sensitivity of 87% and specificity of 57% for detecting PE, with a similar area under the curve as the HU (0.79 ± 0.06 vs. 0.84 ± 0.07; p = 0.21). These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.

Keywords

dual-energy X-ray absorptiometry / mouse model / neurogenic pulmonary edema / subarachnoid hemorrhage

Cite this article

Download citation ▾
Tatsushi Mutoh, Hiroaki Aono, Yushi Mutoh, Tatsuya Ishikawa. Dual-energy X-ray absorptiometry for detecting neurogenic pulmonary edema in a mouse model of subarachnoid hemorrhage. Animal Models and Experimental Medicine, 2025, 8(6): 1146-1151 DOI:10.1002/ame2.70019

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006; 354(4): 387-396.

[2]

Narayan SK, Grace Cherian S, Babu Phaniti P, Babu Chidambaram S, Rachel Vasanthi AH, Arumugam M. Preclinical animal studies in ischemic stroke: challenges and some solutions. Animal Model Exp Med. 2021; 4(2): 104-115.

[3]

Li Y, Zhang J. Animal models of stroke. Animal Model Exp Med. 2021; 4(3): 204-219.

[4]

Zhang JH. Vascular neural network in subarachnoid hemorrhage. Transl Stroke Res. 2014; 5(4): 423-428.

[5]

Plesnila N. Pathophysiological role of global cerebral ischemia following subarachnoid hemorrhage: the current experimental evidence. Stroke Res Treat. 2013; 2013: 651958.

[6]

Guo L, Yang X, Yang B, Tang G, Li C. Prevalence, in-hospital mortality, and factors related to neurogenic pulmonary edema after spontaneous subarachnoid hemorrhage: a systematic review and meta-analysis. Neurosurg Rev. 2023; 46(1): 169.

[7]

Mutoh T, Mutoh T, Taki Y, Ishikawa T. Takotsubo cardiomyopathy as a neurocardiogenic injury after subarachnoid hemorrhage: hemodynamics and fluid management. In: Kirali MK, ed. Cardiomyopathies. InTech Publisher; 2016.

[8]

Parker JC, Townsley MI. Evaluation of lung injury in rats and mice. Am J Physiol Lung Cell Mol Physiol. 2004; 286(2): L231-L246.

[9]

Kanat A, Tsianaka E, Gasenzer ER, Drosos E. Some interesting points of competition of x-ray using during the greco-ottoman war in 1897 and development of neurosurgical radiology: a reminiscence. Turk Neurosurg. 2022; 32(5): 877-881.

[10]

Gargiulo S, Gramanzini M, Megna R, et al. Evaluation of growth patterns and body composition in c57bl/6j mice using dual energy x-ray absorptiometry. Biomed Res Int. 2014; 2014: 253067.

[11]

Kim HS, Jeong ES, Yang MH, Yang SO. Bone mineral density assessment for research purpose using dual energy x-ray absorptiometry. Osteoporos Sarcopenia. 2018; 4(3): 79-85.

[12]

Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised european consensus on definition and diagnosis. Age Ageing. 2019; 48(1): 16-31.

[13]

Bredella MA, Ghomi RH, Thomas BJ, et al. Comparison of dxa and ct in the assessment of body composition in premenopausal women with obesity and anorexia nervosa. Obesity (Silver Spring). 2010; 18(11): 2227-2233.

[14]

Bühler D, Schuller K, Plesnila N. Protocol for the induction of subarachnoid hemorrhage in mice by perforation of the circle of willis with an endovascular filament. Transl Stroke Res. 2014; 5(6): 653-659.

[15]

Flecknell P. Anaesthetic and analgesic agents. In: Flecknell P, ed. Laboratory Animal Anaesthesia and Analgesia. Academic Press; 2023: 51-90.

[16]

Mutoh T, Mutoh T, Sasaki K, et al. Value of three-dimensional maximum intensity projection display to assist in magnetic resonance imaging (MRI)-based grading in a mouse model of subarachnoid hemorrhage. Med Sci Monit. 2016; 22: 2050-2055.

[17]

Mutoh T, Tochinai R, Aono H, Kuwahara M, Taki Y, Ishikawa T. Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice. Animal Model Exp Med. 2024; 7(1): 77-81.

[18]

Tochinai R, Suzuki T, Tomita K, et al. Localized pulmonary vascular changes in a mouse model of subarachnoid hemorrhage created by combination of filament perforation and blood injection. Microvasc Res. 2025; 160: e104810.

[19]

Mutoh T, Kazumata K, Ueyama-Mutoh T, Taki Y, Ishikawa T. Transpulmonary thermodilution-based management of neurogenic pulmonary edema after subarachnoid hemorrhage. Am J Med Sci. 2015; 350(5): 415-419.

[20]

Vespa PM, Bleck TP. Neurogenic pulmonary edema and other mechanisms of impaired oxygenation after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2004; 1(2): 157-170.

[21]

Pennati F, Leo L, Ferrini E, et al. Micro-ct-derived ventilation biomarkers for the longitudinal assessment of pathology and response to therapy in a mouse model of lung fibrosis. Sci Rep. 2023; 13(1): 4462.

[22]

Mecozzi L, Mambrini M, Ruscitti F, et al. In-vivo lung fibrosis staging in a bleomycin-mouse model: a new micro-ct guided densitometric approach. Sci Rep. 2020; 10(1): 18735.

[23]

Chen J, Qian C, Duan H, et al. Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats. J Pineal Res. 2015; 59(4): 469-477.

[24]

Chen S, Zhu Z, Klebe D, et al. Role of p2x purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats. PLoS One. 2014; 9(2): e89042.

[25]

Cobelens PM, Tiebosch IA, Dijkhuizen RM, et al. Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage. Crit Care. 2010; 14(4): R157.

[26]

Fujii M, Sherchan P, Soejima Y, Doycheva D, Zhao D, Zhang JH. Cannabinoid receptor type 2 agonist attenuates acute neurogenic pulmonary edema by preventing neutrophil migration after subarachnoid hemorrhage in rats. Acta Neurochir Suppl. 2016; 121: 135-139.

[27]

Suzuki H, Sozen T, Hasegawa Y, et al. Subarachnoid hemorrhage causes pulmonary endothelial cell apoptosis and neurogenic pulmonary edema in mice. Acta Neurochir Suppl. 2011; 111: 129-132.

[28]

Suzuki H, Sozen T, Hasegawa Y, Chen W, Zhang JH. Caspase-1 inhibitor prevents neurogenic pulmonary edema after subarachnoid hemorrhage in mice. Stroke. 2009; 40(12): 3872-3875.

[29]

Wang G, Hou G, Tian Q, et al. Inhibition of s100a9 alleviates neurogenic pulmonary edema after subarachnoid hemorrhage. Biochem Pharmacol. 2023; 218: 115905.

[30]

Zeng H, Fu X, Cai J, et al. Neutrophil extracellular traps may be a potential target for treating early brain injury in subarachnoid hemorrhage. Transl Stroke Res. 2022; 13(1): 112-131.

[31]

Walder B, Bründler MA, Tötsch M, Elia N, Morel DR. Influence of the type and rate of subarachnoid fluid infusion on lethal neurogenic pulmonary edema in rats. J Neurosurg Anesthesiol. 2002; 14(3): 194-203.

[32]

Zhang L, Jin J, Yao J, et al. Effects of propofol on excitatory and inhibitory amino acid neurotransmitter balance in rats with neurogenic pulmonary edema induced by subarachnoid hemorrhage. Neurocrit Care. 2016; 24(3): 459-471.

[33]

Cole CL, Beck CA, Robinson D, et al. Dual energy x-ray absorptiometry (dexa) as a longitudinal outcome measure of cancer-related muscle wasting in mice. PLoS One. 2020; 15(6): e0230695.

[34]

Kishi K, Goto M, Tsuru Y, Hori M. Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy x-ray absorptiometry in diabetic mice. Exp Anim. 2023; 72(1): 68-76.

[35]

Mutoh T, Kazumata K, Kobayashi S, Terasaka S, Ishikawa T. Serial measurement of extravascular lung water and blood volume during the course of neurogenic pulmonary edema after subarachnoid hemorrhage: initial experience with 3 cases. J Neurosurg Anesthesiol. 2012; 24(3): 203-208.

[36]

Mutoh T, Sasaki K, Moroi J, Ishikawa T. Volumetric patterns and prognosis of neurogenic pulmonary edema after subarachnoid hemorrhage. Am J Respir Crit Care Med. 2023; 2013: 207A3465.

[37]

Sirinoglu D, Sarigul B, Kanat A, Aydin MD, Demirtas R. Interaction between neurogenic pulmonary edema and thoracic 3 DRG degeneration following spinal subarachnoid hemorrhage: first experimental study. J Neurol Surg A Cent Eur Neurosurg. 2024.

RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

AI Summary AI Mindmap
PDF

8

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/