A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state

摘要

An animal model involving stepwise occlusion of the common carotid arteries (sCCAO) in DBA/2 mice is presented in which the right and left carotid arteries were permanently ligated within a time interval of four weeks. Thereafter, cerebral functional and structural parameters were determined at acute (15 min) and subchronic (1 day; 3, 7, and 14 days) time points after sCCAO. Quantitative changes in regional cerebral blood flow (rCBF) as determined by the [14C]iodoantipyrine method, energy state (ATP, phosphocreatine, ADP, AMP, adenosine) as shown by HPLC, brain histopathology, and neuronal densities were measured in both hemispheres. Acute sCCAO was accompanied by a drastic reduction in cerebral energy-rich phosphate concentrations, ATP and phosphocreatine, and in rCBF of more than 50%. In contrast, cortical adenosine increased around five-fold. Subchronic sCCAO, however, was associated with normalization in brain energy metabolites and near-complete restoration of rCBF, except in the caudate nucleus (−40%). No marked signs of necrotic or apoptotic cell destruction were detected. Thus, during the subchronic period, compensatory mechanisms are induced to counteract the drastic changes seen after acute vessel occlusion. In conclusion, this sCCAO mouse model may be useful for long-lasting investigations of stepwise deterioration contributing to chronic cerebrovascular disorders.