Su Xu1,2, Jaylyn Waddell3, Wenjun Zhu1,2, Da Shi1, Andrew D Marshall1,2, Mary C McKenna3, Rao P Gullapalli1,2. 1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 2. Core for Translational Research in Imaging @ Maryland, University of Maryland School of Medicine, Baltimore, Maryland, USA. 3. Department of Pediatrics and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Abstract
PURPOSE: This study evaluated the longitudinal metabolic alterations after neonatal hypoxia-ischemia (HI) in rats and tested the neuroprotective effect of acetyl-L-carnitine (ALCAR) using in vivo proton short-TE Point-RESolved Spectroscopy method. METHODS: Rice-Vannucci model was used on 7-day-old Sprague-Dawley rats. Data were acquired from contralateral and ipsilateral cortex and hippocampus, respectively at 4 time points (24-h, 72-h, 7-days, 28-days) post-HI. The effect of subcutaneous administration of ALCAR (100 mg/kg) immediately after HI, at 4-h, 24-h, and 48-h post-HI was determined. RESULTS: Significant reductions in glutathione (P < 0.005), myo-inositol (P < 0.002), taurine (P < 0.001), and total creatine (P < 0.005) were observed at 24-h postinjury compared with the control group in the ipsilateral hippocampus of the HI rat pups. ALCAR-treated-HI rats had lower levels of lactate and maintained total creatine at 24-h and had smaller lesion size compared with the HI only rats. CONCLUSION: Severe oxidative, osmotic stress, impaired phosphorylation, and a preference for anaerobic glycolysis were found in the ipsilateral hippocampus in the HI pups at 24-h postinjury. ALCAR appeared to have a neuroprotective effect if administered early after HI by serving as an energy substrate and promote oxidative cerebral energy producing and minimize anaerobic glycolysis.
PURPOSE: This study evaluated the longitudinal metabolic alterations after neonatal hypoxia-ischemia (HI) in rats and tested the neuroprotective effect of acetyl-L-carnitine (ALCAR) using in vivo proton short-TE Point-RESolved Spectroscopy method. METHODS:Rice-Vannucci model was used on 7-day-old Sprague-Dawley rats. Data were acquired from contralateral and ipsilateral cortex and hippocampus, respectively at 4 time points (24-h, 72-h, 7-days, 28-days) post-HI. The effect of subcutaneous administration of ALCAR (100 mg/kg) immediately after HI, at 4-h, 24-h, and 48-h post-HI was determined. RESULTS: Significant reductions in glutathione (P < 0.005), myo-inositol (P < 0.002), taurine (P < 0.001), and total creatine (P < 0.005) were observed at 24-h postinjury compared with the control group in the ipsilateral hippocampus of the HIrat pups. ALCAR-treated-HIrats had lower levels of lactate and maintained total creatine at 24-h and had smaller lesion size compared with the HI only rats. CONCLUSION: Severe oxidative, osmotic stress, impaired phosphorylation, and a preference for anaerobic glycolysis were found in the ipsilateral hippocampus in the HI pups at 24-h postinjury. ALCAR appeared to have a neuroprotective effect if administered early after HI by serving as an energy substrate and promote oxidative cerebral energy producing and minimize anaerobic glycolysis.
Authors: Jonathan J Morgan; Gale A Kleven; Christina D Tulbert; John Olson; David A Horita; April E Ronca Journal: NMR Biomed Date: 2013-01-16 Impact factor: 4.044
Authors: R C Vannucci; J R Connor; D T Mauger; C Palmer; M B Smith; J Towfighi; S J Vannucci Journal: J Neurosci Res Date: 1999-01-15 Impact factor: 4.164
Authors: Marco Onofrj; Fausta Ciccocioppo; Sara Varanese; Antonio di Muzio; Menotti Calvani; Santina Chiechio; Maurizio Osio; Astrid Thomas Journal: Expert Rev Neurother Date: 2013-08 Impact factor: 4.618