Akgören N, Dalgaard P, Lauritzen M
Department of Clinical Neurophysiology, Rigshospitalet, University of Copenhagen, Denmark.
Brain Res. 1996 Feb 26;710(1-2):204-14. doi: 10.1016/0006-8993(95)01354-7.
The purpose of this study was to examine mechanisms involved in the coupling of neuronal activity to cerebral blood flow (CBF). CBF was measured in rat cerebellum using laser-Doppler flowmetry during stimulus-evoked neuronal activity and related to the distribution of the extracellular field potential. Local electrical stimulation of the cerebellar cortex activated a narrow beam of parallel fibers (PFs) 100 microns across and evoked increases of CBF along (On-B) and perpendicular (Off-B) to the beam. Increases of CBF and field potentials were recorded for a distance of up to 1500 microns along the activated beam, and perpendicular to the beam, in a zone approximately 1000 microns wide, i.e. about 10 times wider than the zone in which synaptic excitation took place. CBF increased as a function of stimulus frequency up to 75 Hz, the response being larger On-B than Off-B. TTX abolished both the field potentials and the CBF responses at all frequencies, suggesting that action potentials were mechanistically related to the evoked CBF increases. CBF changes were unchanged by picrotoxin, a blocker of GABA(A) receptors, consistent with the idea that inhibitory synaptic activity does not contribute to CBF increases. The latency to the CBF rise was much shorter On-B than Off-B for the same distance from the stimulating electrode. This may suggest that the CBF response Off-B is dependent on diffusion of vasoactive substances from neuronal structures activated by the parallel fibers On-B. Nitric oxide (NO) synthase inhibition with NG-nitro-L-Arginine increased the time latency to onset of CBF rise by 2-4 times and attenuated the evoked CBF increase by approximately 50%. Sodium nitroprusside, a NO donor, increased baseline CBF, but did not reverse the effects of L-NNA. Thus the initial part of the evoked CBF rise is probably mediated by NO, which also contributes to the later part of the response. This study provides insight into the distribution and mechanism of neurally evoked increases of CBF, of putative importance for the interpretation of activation studies in animals and humans.
本研究的目的是探讨神经元活动与脑血流量（CBF）耦合所涉及的机制。在刺激诱发的神经元活动期间，使用激光多普勒血流仪测量大鼠小脑的CBF，并将其与细胞外场电位的分布相关联。小脑皮质的局部电刺激激活了一束宽100微米的平行纤维（PFs），并引起沿该束平行方向（On-B）和垂直方向（Off-B）的CBF增加。沿着激活束并垂直于该束，在一个约1000微米宽的区域内，记录到CBF和场电位增加的距离可达1500微米，即大约比发生突触兴奋的区域宽10倍。CBF随着刺激频率增加至75 Hz而增加，On-B方向的反应比Off-B方向更大。河豚毒素（TTX）在所有频率下均消除了场电位和CBF反应，表明动作电位在机制上与诱发的CBF增加有关。GABA(A)受体阻滞剂印防己毒素对CBF变化无影响，这与抑制性突触活动对CBF增加无贡献的观点一致。对于距刺激电极相同距离，On-B方向CBF上升的潜伏期比Off-B方向短得多。这可能表明Off-B方向的CBF反应依赖于血管活性物质从On-B方向平行纤维激活的神经元结构扩散而来。用NG-硝基-L-精氨酸抑制一氧化氮（NO）合酶可使CBF上升开始的时间潜伏期增加2 - 4倍，并使诱发的CBF增加减弱约50%。NO供体硝普钠增加了基线CBF，但并未逆转L-NNA的作用。因此，诱发的CBF上升的初始部分可能由NO介导，NO也对反应的后期部分有贡献。本研究深入了解了神经诱发的CBF增加的分布和机制，这对解释动物和人类的激活研究可能具有重要意义。
