N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury

To evaluate the contribution of cellular dysfunction and neuronal loss to b rain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of m icrospheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA dep letion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and ever y 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), r espectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA s triatal content was observed despite the lack of tissue necrosis. Overall r esults show that cellular dysfunction can cause higher reductions in NAA le vel than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.