Heiss W D, Grond M, Thiel A, Ghaemi M, Sobesky J, Rudolf J, Bauer B, Wienhard K
Max-Planck-Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Germany.
Stroke. 1998 Feb;29(2):454-61. doi: 10.1161/01.str.29.2.454.
Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas.
In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke.
In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow.
These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.
急性缺血性脑卒中的治疗只有在神经元存活且组织未发生梗死时才会有效。由于γ-氨基丁酸受体在皮质中大量存在且对缺血损伤敏感，其亚基（即中枢苯二氮䓬受体，BZR）的特异性放射性配体可能有助于作为神经元完整性的指标以及不可逆损伤的标志物。为验证这一假设，我们研究了缺血性脑卒中后早期BZR配体[11C]氟马西尼（FMZ）的结合情况，并与最终梗死灶范围及皮质低代谢区域进行比较。
对10例首次发生半球性卒中的患者，在发病3.5至16小时后通过正电子发射断层扫描研究脑血流量、脑氧代谢率（CMRO₂）、氧摄取分数（OEF）及FMZ结合情况。将血流、氧代谢及FMZ结合的早期变化与葡萄糖代谢的永久性紊乱进行比较，并在卒中后12至22天通过MRI或CT确定最终梗死灶的大小。
除1例患者外，所有患者的脑血流量均受到干扰，8例患者脑血流量显著降低，1例患者出现与神经功能缺损部位相对应的血流灌注增加。在这些区域，CMRO₂也有所降低，但程度不一，导致OEF变化很大。CMRO₂显著降低（<60微摩尔/100克每分钟）的区域与FMZ结合降低（<白质平均值的4.0倍）的区域相对应。在所有患者中，早期FMZ图像上均可看到最终的皮质梗死灶。尽管OEF范围很广，但通过降低的FMZ结合可将梗死灶与未梗死的皮质区分开来。在最终发生低代谢的皮质区域，FMZ结合最初降低或正常，OEF范围很广；这表明神经元丢失和/或失活是代谢紊乱的原因。此外，注射后最初2分钟内FMZ分布与局部脑血流量之间存在高度显著的相关性。
这些结果表明，卒中后早期通过降低的FMZ结合可检测到永久性和不可逆损伤的皮质。由于FMZ分布还可显示局部脑灌注情况，BZR放射性配体在急性缺血性脑卒中患者中具有作为临床有用示踪剂的潜力。这些示踪剂提供的组织损伤证据可能与个体治疗策略的选择有关。
