THE ROLE OF SPREADING DEPRESSION IN FOCAL ISCHEMIA EVALUATED BY DIFFUSION MAPPING

This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occ lusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCI group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes follo wing MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15-minute intervals, evaluated by continuous ap parent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15-minute time epo chs with a single SD episode (36.5 +/- 12.9 mm(3), mean +/- SD) or mul tiple SD episodes (39.8 +/- 22.3) compared with those without SD (13.9 +/- 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after M CAO was significantly larger in the KCI group, with more total SDs (23 7.8 +/- 13.8) than the NaCl group (190.5 +/- 12.6) (p = 0.0001). This study demonstrates that ischemia-related and induced SDs increase sign ificantly ischemic lesion volume in vivo, supporting the hypothesis fo r a causative role of SD in extending focal ischemic injury.