The Cerebral Injury At Acute Stage After Subarachnoid Hemorrhage And Its Possible Mechanism In Rabbits

Background and purpose: Subarachnoid hemorrhage (SAH) is a common and serious disease, which is a kind of pathologic state of the blood from intracranial aneurysm rupture with nonexternal-injuriing into subarachnoid cavity. Its morbidity is 15% and 10/100000*year in stroke persons with spontaneous intracranial hemorrhage and in the crowd, respectively. Cerebral vasospasm has long been considered the severe complication after SAH, which there is no positive method to prevent beforehead and treat effectively. Its morbidity is around 30%~90% and 40% will die. Despite the progress in understanding its pathophysiology and the significant improvement in clinical outcome following treatment of intracranial aneurysm rupture with nimodipine and triple-H therapy, there is still a high incidence with functional impairment of nervousness and cognition in survived person. All these indicate that the course of cerebral vasospasm and delayed ischemic neurological deficits (DIND) remain unchanged. The aim of the present study is to 1)explore the dynamic alterations of cerebral microcirculation and water diffusion before and after SAH with the advanced imaing techniques.2) probe the related pathologic mechinism by analyzing the relationship between the ADC value and perfusion parameters. Besides, the relationship between the cerebral vasospasm and cerebral microcirculation is analyzed to provide the theoretical basis for therapy and prevention beforehand.Methods: Rabbit SAH model was established by a two-hemorrhage method (blood injection into the prechiasmatic cistern). Forty-eight adult New-Zealand rabbits of either sex, weighing 1500-2500g were involved in this study. All animals were randomly assigned into 2 groups: model group (n=24) and control group ( n=24). According to observation time and imaging modality, these two groups were randomly subdivided into 6 groups: CTP 5, 30, 45, 60 and 90 minutes group and ADC continuious observation group, 4 animals in each group. One-stop check of CT plain scan, CT perfusion and CTA was performed at 5 min, 30min, 45 min, 60 min and 90 min after the 1st and 2nd operation; MR diffusion weighted imaging was performed in ADC group at the same observation time after operation until 90 minutes and routine T1WI, T2WI, FLAIR, 3D time-of-flight MRA images were obtained at the intermission. The CBF, CBV, MTT and ADC maps were then obtained and the related parameters were calculated. If there were animals died during experiment, additional animals would be supplied at once.All data was analyzed by SPSS 10.0 statistical software package. Test of normality and one-way ANOVA were performed among groups. Differences with P<0.05 were considered significant.Results:The successful rate of model establishement is 91.67%(after the 1st blood injection). CT images could demonstrate the hemorrhage as increased attenuation throughout the subarachnoid space. Hemorrhage could also be seen in cerebral ventricles in some animals, and the cerebral ventricles dilatation could also be observed. Those changes were obvious after the 2nd blood injection. FLAIR MR images demonstrated SAH in all model animals (100%) even in negative CT . The blood clots predominantly located in the posterior fossa and spinal subarachnoid space of the upper cervical segments, which distributed around the brainstem and upper cervical cord. The basilar cistern was filled with blood clots, and the basal artery, the terminals of bilateral vertebral arteries were covered with blood clots. Only small blood clots located around the circle of Willis and the intracranial segments of bilateral internal carotid arteries. Little blood clots can be seen in the surface of bilateral hemisphere.In model group,the abnormal diffusion aera spreaded gradually from 5min to 60min after the 1st blood injection, and the ADC values in bilateral cerebral cortex were obviously lower than those in normal before operation[0.9835±0.1066(×10-3 mm2/s)], which were 0.9219±0.0953(×10-3mm2/s), 0.9230±0.0768(×10-3mm2/s), 0.9213±0.0946×10-3mm2/s), 0.9288±0.0914(×10-3 mm2/s) from 5min to 60min group, respectively(P=0.000).The abnormal ADC area recovered but still had signifcant difference from the normal at 90min (P=0.003). The ADC value in bilateral basal ganglia had no signifcant difference from the normal(P=0.743).No difference of the ADC was found between bilateral cerebral cortex from 5min to 45min after the 2nd blood injection and normal ( P=0.142, 0.266, 0.280), but the ADC value 60min to 90min after the 2nd blood injection in bilateral cerebral cortex was lower than the normal with great significance(P=0.000).The change, recovered gradually at 90 min. The ADC value in basal ganglia had no significant difference from the normal and those in control, which had reduced significantly at 60min and 90min(P=0.000, 0.001). No ADC changes were demonstrated in control group compared with normal before operation at the same observion time point (P=0.788).CBF, CBV in cerebral cortex had an obvious increase 5~45min after the 1st blood injection into the prechiasmatic cistern, which were great higher than those in normal and control group(P=0.000) and reduced mildly but still higher than those in other groups at 90min. MTT was significantly longer than that in normal and control group (MTT at 5 min after the 1st blood injection, before operation and control group is 4.39±1.53s, 3.93±1.20s, 3.74±0.81s, respectively; P=0.035, 0.002). CBF and CBV in the same region reduced slightly at 30 min and 45 min, but still obviously higher than those in normal and control group. MTT had no significant differences from that in normal and control group at 30min(P=1.000), but became longer at 45min,compared with normal(P=0.000). CBF and CBV in bilateral cerebral cortex had a less elevation after the 2nd blood injection than after the 1st one, and its amplitude decreased. The increases of CBF, CBV were diffuse throughout the brain, and the change in basal ganglia was similar to cerebral cortex at the acute stage after SAH.CT angiography indicated that the diameter of the basal artery was slimmer than those in normal from 5min to 90min by( reduced by 10.05%, 22.59%, 18.12%, 12.71%, 6.68% at each time point respectively). Among which the most predominant changes happened at 30min and 45min. Similar changes happened and more noticeablely than the 1st blood injection after the 2nd. The diameter reduced by 15.78%, 28.68%, 16.15%, 8.10%, 7.70%, respectively. These changes of vasospasm relieved in some degrees during 60min~90min time.Conclusions:1. The SAH mode establishment method used in this study(Two-hemorrhage injection through prechiasmatic cistern)had a high successful rate.2. There exsists the cerebral injury at acute stage after SAH,which can be monitored by MR diffusion imaging both spatially and temporally.The change of ADC value is correlated with the seriousiness of injury after SAH.3. There is an increase of the perfusion in regions of injury but rather decrease.CT perfusion is a fast and reliable brain imaging modality in measurement of cerebral haemodynamics continuously before and after SAH.4. The toxic effect of blood clots distributed in the subarachnoid space may be the major reason that leads to cerebral cortex tissue metabolism depression and cortical spreading depression (CSD) instead of hypoperfusion.5.CTA can be used to evaluatef the cerebral vasospasm. MRA is helpful in the diagnosis of CVS, its value is limitted.