A Protocol for Simultaneous In Vivo Imaging of Cardiac and Neuroinflammation in Dystrophin-Deficient MDX Mice Using [ 18 F]FEPPA PET.
Joanne M TangAndrew McClennanLinshan LiuJennifer HadwayJohn A RonaldJustin W HicksLisa HoffmanUdunna C AnazodoPublished in: International journal of molecular sciences (2023)
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss-notably within muscles and the central neurons system. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies have improved life expectancy; however, this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, better assessment of dystrophic heart and brain pathophysiology is needed. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration; however, neuroinflammation's role is largely unknown in DMD despite being prevalent in other neurodegenerative diseases. Here, we present an inflammatory marker translocator protein (TSPO) positron emission tomography (PET) protocol for in vivo concomitant assessment of immune cell response in hearts and brains of a dystrophin-deficient mouse model [ mdx:utrn (+/-)]. Preliminary analysis of whole-body PET imaging using the TSPO radiotracer, [ 18 F]FEPPA in four mdx:utrn (+/-) and six wildtype mice are presented with ex vivo TSPO-immunofluorescence tissue staining. The mdx:utrn (+/-) mice showed significant elevations in heart and brain [ 18 F]FEPPA activity, which correlated with increased ex vivo fluorescence intensity, highlighting the potential of TSPO-PET to simultaneously assess presence of cardiac and neuroinflammation in dystrophic heart and brain, as well as in several organs within a DMD model.
Keyphrases
- duchenne muscular dystrophy
- pet imaging
- positron emission tomography
- heart failure
- left ventricular
- late onset
- computed tomography
- muscular dystrophy
- mouse model
- cerebral ischemia
- lipopolysaccharide induced
- respiratory failure
- randomized controlled trial
- traumatic brain injury
- early onset
- high fat diet induced
- white matter
- atrial fibrillation
- multiple sclerosis
- mechanical ventilation
- pet ct
- oxidative stress
- intensive care unit
- cognitive impairment
- high resolution
- extracorporeal membrane oxygenation
- high intensity
- spinal cord
- adipose tissue
- metabolic syndrome
- type diabetes
- wild type
- climate change
- binding protein
- cardiac resynchronization therapy
- mass spectrometry