In Vivo Longitudinal Proton Magnetic Resonance Spectroscopy on Neonatal Hypoxic-Ischemic Rat Brain Injury: Neuroprotective Effects of Acetyl-L-Carnitine

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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. Magn Reson Med 74:1530–1542, 2015. © 2014 Wiley Periodicals, Inc.

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