Nitric Oxide Scavenging by Hemoglobin or Nitric Oxide Synthase Inhibition by N -Nitro-L-Arginine Induces Cortical Spreading Ischemia When K + Is Increased in the Subarachnoid Space

作者：Jens Peter Dreier, K Körner, Natalie Ebert, Astrid Görner, Inger Rubin, Tobias Back, Ute Lindauer, Tilo Wolf, Arno Villringer, Karl M. Einhäupl, Martin Lauritzen, Ulrich Dirnagl · 发表于：Journal of Cerebral Blood Flow & Metabolism · 年份：1998 · DOI：10.1097/00004647-199809000-00007 · 被引用次数：292 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Nitric Oxide and Endothelin Effects、Intracranial Aneurysms: Treatment and Complications

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide (NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin (Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14+/-7% (n=4) compared with the baseline (100%). The ischemic events lasted for 53+/-17 minutes and were associated with a negative subarachnoid DC shift of -7.3+/-0.6 mV of 49+/-12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine (L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n=5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n=4), [K+]ACSF at 3 mmol/L combined with L-NA (n=10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four anim...