Dohmen C, Kumura E, Rosner G, Heiss W D, Graf R
Max-Planck-Institut für Neurologische Forschung, Köln, Germany.
J Cereb Blood Flow Metab. 2001 May;21(5):503-10. doi: 10.1097/00004647-200105000-00004.
In vitro studies suggest that adenosine may attenuate anoxic white matter damage as an intrinsic protective substance. The authors investigated ischemic alterations of purines in relation to tissue depolarization and extracellular calcium and amino acid concentrations in vivo using microdialysis and ion-selective electrodes in cortical gray and subcortical white matter of 10 cats during 120 minutes of global brain ischemia. Immediately on induction of ischemia, regional cerebral blood flow ceased in all cats in both gray and white matter. The direct current potential rapidly decreased, the decline being slower and shallower in white matter. Extracellular calcium levels decreased in gray matter. In contrast, they first increased in white matter and started to decrease below control levels only after approximately 30 minutes. Adenosine levels transiently increased in both tissue compartments; the peak was delayed by 30 minutes in white matter. Thereafter, levels declined faster in gray than in white matter and remained elevated in the latter tissue compartment. Inosine and hypoxanthine elevations were progressive in both regions but smaller in white matter. Levels of gamma-aminobutyric acid, another putatively protective agent, steadily increased, starting immediately in gray matter and delayed by almost 1 hour in white matter. The delayed and prolonged accumulation of adenosine correlates with a slower adenosine triphosphate breakdown in white matter ischemia and may result in protection of white matter by suspending cellular calcium influx.
体外研究表明，腺苷作为一种内源性保护物质，可能减轻缺氧性白质损伤。作者在10只猫的大脑皮质灰质和皮质下白质中，采用微透析和离子选择性电极，在120分钟全脑缺血期间，研究了嘌呤的缺血性改变与体内组织去极化、细胞外钙和氨基酸浓度的关系。缺血诱导后立即观察到，所有猫的灰质和白质区域脑血流量均停止。直流电位迅速下降，白质中的下降速度较慢且幅度较小。灰质中的细胞外钙水平降低。相比之下，白质中的细胞外钙水平首先升高，仅在约30分钟后才开始降至对照水平以下。两个组织区室中的腺苷水平均短暂升高；白质中的峰值延迟30分钟出现。此后，灰质中的腺苷水平下降速度比白质快，白质中的腺苷水平仍高于对照水平。两个区域中的肌苷和次黄嘌呤水平均呈进行性升高，但白质中的升高幅度较小。另一种假定的保护剂γ-氨基丁酸水平持续升高，灰质中立即开始升高，白质中延迟近1小时。腺苷的延迟和持续积累与白质缺血时三磷酸腺苷分解较慢有关，可能通过中止细胞钙内流对白质起到保护作用。
