Introduction
Selective neuronal loss occurs after mild and/or short-duration brain ischemia. Since cerebral perfusion reserve (CPR) is one of the mechanism to maintain cerebral blood flow (CBF), its impairment may be a potential risk of selective neuronal loss. In order to clarify potential neuronal loss in the brain areas with impaired CPR, we investigated the relationship between cerebral vasoreactivity and central benzodiazepine receptor density in patients with steno-occlusive lesion of the major intracranial arteries.
Subjects and Methods
The PET and I-123 iomazenil SPECT were performed in 8 patients with unilateral steno-occlusive lesion of the major intracranial arteries. The CPR was measured by means of the PET with O-15 labeled water during resting condition and after acetazolamide loading. The CPR was defined as (acetazolamide-loading CBF-resting CBF)/resting CBFX100(%). The oxygen extraction fraction (OEF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) were also measured. Central benzidiazepine receptor density was measured by the SPECT with I-123 iomazenil. Early (30 min post-injection) and delayed (3 hours post-injection) scans of I-123 iomazenil SPECT were performed. The binding potential (BP) of central benzodiazepine receptor was estimated by creating the image of the distribution volume (Vd) based on the 2-compartment model. After image registration between the PET and Vd images, 11–12 circular regions of interests were located on the affected and unaffected cerebral cortices. The interval between the PET and SPECT study was within 1 week. Relative BP in the affected hemisphere was defined as a lesion-to-contralateral (L/C) ratio of Vd. Disturbed CPR lesion was defined as the areas with the resting CBF below 80% of the unaffected hemisphere with the CPR less than 10%, and relative BP in the lesion was analyzed in relation to the CPR, OEF, and CMRO2.
Results
Mean CBF, CMRO2, OEF, and CPR in the lesion was 26.8±8.6 ml/100 ml/min, 2.07±0.43 ml/100 ml/min, 52±8%, and −4.5±6.7%, respectively. The mean OEF was significantly higher than that of unaffected cortices (42±4.1%, p<0.0001). The mean CMRO2 was significantly lower than that of the unaffected cerebral cortices (2.65±0.46 ml/100 ml/min, p<0.0001). The relative BP of this area (0.94±0.08) was significantly decreased when compared with unity (Wilcoxon t-test, p<0.0001). The relative BP in the areas with OEF more than 55% (0.90±0.07) was significantly lower than that with OEF less than 55% (0.93±0.07, p=0.041).
Discussion
The present results demonstrated that the reduction of CBF and impaired CPR was associated with significant reduction of central benzodiazepine receptor density. Misery perfusion may facilitate loss of central benzodiazepine receptor. The metabolic reduction of the lesion may be due partly to the neuronal loss. Conclusion: Selective neuronal loss occurs in the areas with reduced CBF and impaired perfusion reserve and is accelerated by misery perfusion in patients with steno-occlusive cerebral artery disease.