Zornow M H, Prough D S
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0591, USA.
New Horiz. 1996 Feb;4(1):107-14.
Increases in intraneuronal Ca2+ concentration, which accompany cerebral ischemia and traumatic brain injury, initiate a cascade of biochemical events that can eventually result in cell lysis and death. Calcium-channel blockers, in certain experimental models of focal and global ischemia, attenuate the increase in intracellular Ca2+ concentration and thereby ameliorate neurologic damage. Clinical efficacy varies among disease states. After nontraumatic subarachnoid hemorrhage, nimodipine has become a standard of care. Calcium-channel blockers improve outcome, whether given before or after onset of vasospasm. Although the precise mechanism of their beneficial effect remains unclear (vasodilation vs. attenuation of increases in intracellular Ca2+ concentrations), numerous studies have demonstrated decreased neurologic morbidity. Although there also is suggestive evidence of benefit in human stroke, these results have not been sufficiently impressive to result in the widespread use of these drugs as neuroprotectants. In clinical trials after cardiac arrest, calcium-channel blockers have been ineffective. In clinical traumatic brain injury, data suggest moderate efficacy in younger patients and those with post-traumatic subarachnoid hemorrhage, although overall outcome is not changed. The future role of calcium-channel blockers as neuroprotectants appears bright. Newer classes of compounds, with greater specificity and fewer side effects, may provide greater clinical benefit.
神经元内钙离子浓度的升高与脑缺血和创伤性脑损伤相伴，引发一系列生化事件，最终可能导致细胞溶解和死亡。在某些局灶性和全脑缺血的实验模型中，钙通道阻滞剂可减轻细胞内钙离子浓度的升高，从而改善神经损伤。临床疗效因疾病状态而异。非创伤性蛛网膜下腔出血后，尼莫地平已成为一种标准治疗药物。钙通道阻滞剂无论在血管痉挛发作之前还是之后给药，均可改善预后。尽管其有益作用的确切机制尚不清楚（血管舒张与细胞内钙离子浓度升高的减轻），但大量研究已表明神经发病率降低。虽然也有提示性证据表明其对人类中风有益，但这些结果并未令人印象深刻到足以使这些药物作为神经保护剂得到广泛应用。在心脏骤停后的临床试验中，钙通道阻滞剂无效。在临床创伤性脑损伤中，数据表明在年轻患者和创伤后蛛网膜下腔出血患者中疗效中等，尽管总体预后并未改变。钙通道阻滞剂作为神经保护剂的未来作用似乎很光明。具有更高特异性和更少副作用的新型化合物可能会带来更大的临床益处。
