N-Acetylaspartate to Total Creatine Ratio in the Hippocampal CA1 Sector after Transient Cerebral Ischemia in Gerbils: Influence of Neuronal Elements, Reactive Gliosis, and Tissue Atrophy

Abstract

The authors compared temporal profiles of Nacetylaspartate (NAA) and the NAA/total creatine ratio with neuronal and astrocytic densities and with tissue atrophy in the hippocampal CA1 sector of gerbils after 5-minute bilateral forebrain ischemia and subsequent reperfusion for up to 6 months. The CA1 sector was dissected from 20-μm lyophilized sections (n = 5) for NAA, phosphocreatine, and creatine assays using high-performance liquid chromatography. Adjacent 10-μm sections were used for immunohistochemical analysis to follow neuronal and astrocytic responses. The NAA concentration was significantly ( P<0.01) decreased after 7 days but leveled off thereafter. The NAA/total creatine (phosphocreatine + creatine) ratio was significantly decreased after 7 days and further decreased ( P<0.05) after 6 months. Extensive neuronal damage developed beyond 7 days, while reactive astrogliosis progressed throughout the observation period. There was a good linear correlation ( P<0.01) between astroglial density and the NAA/total creatine ratio beyond 7 days. The thickness of the CA1 sector was significantly reduced after 1 month and further reduced after 6 months. Although both NAA level and the NAA/total creatine ratio seemed to be indicators of neuronal damage, the latter could be influenced by reactive astrogliosis with progression of tissue atrophy.