Phosphate-related energy compounds are not exhausted in chronically hypoperfused rat brain cortex after cortical spreading depression

Long-term bilateral common carotid occlusion (BCCAO) in rats induces brain hypoperfusion and structural injury, and could have relevance as a model of vascular dementia in which cortical metabolism is reduced. The present study was designed to assess whether phosphate-related energy compounds and blood supplies are markedly affected by KCI-induced cortical spreading depression (CSD), which leads to metabolic and cerebral blood flow changes in rats with chronic BCCAO, by means of near-infrared spectroscopy and phosphorus magnetic resonance spectroscopy. Male Wistar rats were divided into 4 groups: BCCAO for 1 week (n = 6) and 4 weeks (n = 15), and sham operation for 1 week (n = 7) and 4 weeks (n = 7). The phosphocreatine (Pcr) index (PCr/PCr+Pi) and intracellular pH (pHi) were measured pre-CSD, just after KCl application, and at 20 and 40 minutes after CSD. Brains were evaluated by histology with hematoxylin and eosin and immunohistochemical reaction for glial fibrillary acidic protein (GFAP). Rapid signal changes of oxy-, deoxy-, and total hemoglobin were observed in all KCl-applied brains. The PCr index and pHi values in BCCAO were not different than those in control rats. The percentage of vacuolated area in the optic tract and percentage values of GFAP-positive area in the frontoparietal cortex were significantly increased in BCCAO. The generation of CSD was seen in regions of cortical gliosis induced by BCCAO, and severe energy exhaustion did not occur during or after CSD. Our results may suggest that the functional interaction of neurons and glia is sustained even in brain tissue where the metabolic state of neurons is impaired and astrocytes are proliferated.