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Reversible Loss of N-Acetylaspartate After 15-Min Transient Middle Cerebral Artery Occlusion in Rat: A Longitudinal Study with In Vivo Proton Magnetic Resonance Spectroscopy

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Abstract

It is generally accepted that N-acetylaspartate (NAA) can be used a biochemical marker for assessing neuronal viability/integrity after cerebral ischemia. However, this view has recently been questioned based on observations showing that after a photothrombotic permanent ischemia the acute decline of NAA in the infracted regions, where massive neuronal loss persists, is reversible over time. In this study, we measured the longitudinal changes of NAA and total creatine (Cr) in ischemic rat brain after a 15-min transient middle cerebral artery occlusion (MCAO) by in vivo 1H magnetic resonance spectroscopy. The results showed that the levels of NAA and total Cr in the ischemic lesion decrease significantly at 1 day post-ichemia, followed by spontaneous recovery to the control levels by 2 weeks and remained stable thereafter up to 16 weeks. The normalization of NAA and total Cr levels was associated histologically with persisted neuronal loss up to 90 % in the ischemic core, and accompanied by marked reactive astrocytic responses occurring with a similar time course. The absolute T2 relaxation time in the ischemic lesion increased during acute phase, and declined afterwards during subacute and chronic phases of 15-min MCAO. The delayed decreases of T2 in the ischemic lesion might be associated with deposition of paramagnetic species, such as manganese and iron originated from chronic inflammation, vascular degradation and/or hemorrhagic transformation. The results of this study give further support to the hypothesis that the recovery of NAA after cerebral ischemia might have contributions from reactive glia cells, and caution the use of NAA as a specific neuronal marker during the chronic stage of cerebral ischemia.

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Acknowledgments

Supported by Natural Science Foundation of China grants 81171302 and 20921004, Chinese Academy of Science key project KJCX2-SW-H12-03 and a 973 grant from the Chinese Ministry of Science and Technology (2011CB707802).

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No potential conflicts of interest are disclosed.

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Authors and Affiliations

  1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, 30# Xiaohongshan, Wuhan, Hubei, 430071, China

    Junchao Qian & Hao Lei

  2. High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China

    Junchao Qian

  3. Department of Neurology, Anqing Hospital of Anhui Medical University, Anqing, 246003, China

    Baojin Qian

Authors
  1. Junchao Qian
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  2. Baojin Qian
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  3. Hao Lei
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Corresponding author

Correspondence to Hao Lei.

Additional information

Junchao Qian and Baojin Qian contributed equally to this work.

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Qian, J., Qian, B. & Lei, H. Reversible Loss of N-Acetylaspartate After 15-Min Transient Middle Cerebral Artery Occlusion in Rat: A Longitudinal Study with In Vivo Proton Magnetic Resonance Spectroscopy. Neurochem Res 38, 208–217 (2013). https://doi.org/10.1007/s11064-012-0910-2

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  • DOI: https://doi.org/10.1007/s11064-012-0910-2

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