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  • Early diagnosis of CVS and DCI is a key


    Early diagnosis of CVS and DCI is a key issue in the management of SAH patients. In this regard, CT Perfusion (CTP) is the most accurate and sensitive method for noninvasive imaging assessment of cerebral ischemia with a great value for prediction and early diagnosis of CVS and DCI. CTP is a relatively new technique that uses complex deconvolution algorithms and related software to generate perfusion maps that can assess cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) which can be used to qualitatively and quantitatively evaluate cerebral perfusion in a time-sensitive manner. Previous clinical and animal studies have demonstrated the positive effects of BQ123 in central nervous system diseases. BQ123 can improve early inflammatory response, promote motor recovery after spinal cord injury, prevent the later development of central sensitization, block experimental cerebral malaria-induced neurocognitive impairments, impede the formation and spread of seizure to a great degree (Guo et al., 2014, Tai et al., 2013, Freeman et al., 2016, Gulati, 2016, Erdogan et al., 2014). BQ-123 is a specific endothelin receptor A antagonist. By blocking ET-1 receptors BQ-123 could reduce vasospasm and inhibit both the sympathetic nervous system and renin angiotensin system activity, offering its promising therapeutic potential for vascular diseases such as stroke (Barone et al., 2000, Legos et al., 2008). In this study, we set out to characterize the time course of hemodynamics and ET-1 in different Irinotecan HCl Trihydrate regions with BQ123 intervention in experimental SAH, and to evaluate the specific role of endothelin-1 receptor antagonist in SAH.
    Discussion In the present study, we focused on the role of ET-1 in SAH and our data indicated that the BQ-123 administered intracisternally increases the microcirculatory blood flow in the rabbit model of SAH and results in brain tissue protection as demonstrated in the histological findings. Our results further showed that in rabbit SAH model, the perfusion of brain microcirculation on the first and 4th days after administration of BQ-123 was significantly improved, as demonstrated by a significant increase in CBF, and a prolonged shortening of MTT. Intracisternal administration of ET-1 antagonist BQ-123 significantly improved cerebral microcirculation during the early stage of SAH, indicating that timing for interfering with ET-1 blocker is critical. Acute vasospasm, despite it appeared to be short-lived, could be reduced to an extent that the delayed vasospasm could be prevented or attenuated (Baldwin et al., 2004). However, we also noticed that on the 7th day after the drug administration, the MTT was significantly longer than the first day, and the CBF also decreased even though these changes seemed to be much minor than that in MTT. We also noticed that there was a rebound in MTT around day 7 after the administration of BQ123 and it is unknown what caused this paradoxical phenomenon. Furthermore, the effect of BQ123 on the 7th day post SAH appeared to tape off when compared with the effects of BQ123 in the previous 4 days. In addition, the effect of BQ123 on the cerebral microcirculation appeared to be lobe dependent. For example, the MTT of the temporal lobe was significantly greater than that of the frontal lobe and parietal-occipital lobe on the first day. On the 4th day, the CBV of the parietal-occipital lobe was significantly higher than any other lobes. These findings strongly suggest that, after SAH has occurred, BQ-123 exerts its more dominant regulatory action on the microcirculation in the parietal-occipital lobe than the other lobes. This region-specific action of BQ-123 on the perfusion is interesting and it could be related to the density and affinity of endothelin receptors in different regions. Bhalla's experiment confirmed density increased and affinity decreased for ETA receptors in the cerebral ischemic region compared to sham 24 h post middle cerebral artery occlusion. However, density of ETA receptors was similar, while affinity in the infarcted hemisphere increased on day 7 (Bhalla et al., 2016). However, it is unclear whether the differential effects of BQ-123 on each lobe's perfusion could affect the functional recovery of neuronal cells in the hypoperfused regions but could partially explains why BQ-123 can reduce mortality after SAH. Additionally, this observation also indicated that the perfusion state and compensation could be differently regulated in the different regions of the brain following SAH, rendering the therapeutic benefits of blocking ET-1 system by administration of BQ-123 to be lobe dependent. Obviously, further studies are required to elucidate the specific mechanisms of ET-1 blockers in the context of acute SAH.