Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2.

Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. Here, we genetically increase P2Y1 receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes of male mice to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression causes neuronal hyperexcitability by increasing both astrocytic and neuronal Ca2+ signals. We identify insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulate P2Y1R and increase IGFBP2. The present findings identify a mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing insights that might be relevant for intervention in diverse neurological disorders.

Iodine-123-Iomazenil Single-Photon Emission Computed Tomography Revealed Recovery of Neuronal Viability in Association With Improvement of Cognitive Dysfunction After Revascularization in Moyamoya Disease.

BACKGROUND AND OBJECTIVES: Recent studies indicate that 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) can demonstrate neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult patients with moyamoya disease (MMD), no standard neuroradiological methods to define such conditions have been established. We examined the relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in patients with MMD. METHODS: The study participants were 16 adult patients with MMD whose cerebrovascular reactivities were decreased only on the surgical sides of combined revascularization. Cognitive function was examined using the Mini-Mental State Examination (MMSE; cutoff: 27) and the Frontal Assessment Battery (FAB; cutoff: 16) before and at 3 to 6 months after surgery. 123I-iodoamphetamine (123I-IMP) SPECT with acetazolamide challenge and 123I-IMZ SPECT were performed concurrently while evaluating cognitive function. The radioreactivities of 123I-IMZ SPECT in regions with decreased cerebrovascular reactivities on 123I-IMP SPECT were investigated using affected-to-contralateral side asymmetry ratio (IMZ-ACR). RESULTS: Twelve patients showed normal cognitive function (MMSE: 29.8 ± 0.4, FAB: 18 ± 0) before surgery. No evident laterality of 123I-IMZ uptake was seen (IMZ-ACR: 0.98 ± 0.04). Neither cognitive function nor 123I-IMZ SPECT worsened after surgery (MMSE: 29.8 ± 0.3, FAB: 18 ± 0, IMZ-ACR: 1.00 ± 0.04). By contrast, 4 patients presented cognitive dysfunction (MMSE: 24.3 ± 3.9, FAB: 14.8 ± 2.7) before revascularization. Preoperative imaging of these patients showed decreased 123I-IMZ uptake, and their IMZ-ACRs (0.83 ± 0.08) were significantly lower than those of the normal group. After revascularization, cognitive functions and 123I-IMZ uptake tended to ameliorate (MMSE: 27.5 ± 1.7, FAB: 16.3 ± 2.2, IMZ-ACR: 0.94 ± 0.09). CONCLUSION: Preoperative cognitive function was associated with 123I-IMZ uptake in adult patients with MMD. After revascularization, cognitive function could be recovered in the viable areas of the brain, which is consistent with 123I-IMZ SPECT findings.

Analysis of vascular perfusion territory using selective intraarterial injection CT angiography before and after revascularization surgery in patients with moyamoya disease.

OBJECTIVE: In moyamoya disease (MMD), blood flow to the internal carotid artery (ICA) system is supplied via the basal fine vascular network, leptomeningeal anastomoses, and transdural collateral vessels from the external carotid artery (ECA). After revascularization, there is a dramatic change in cerebral perfusion to the ECA system. Understanding this shift in blood supply is important for evaluating treatment efficacy and elucidating the postoperative pathophysiology. However, anatomical and quantitative methods for doing so have not yet been established. In the present study, selective intraarterial injection CT angiography (iaCTA) was performed in patients with MMD, and blood supply changes in each arterial system before and after revascularization surgery were evaluated. METHODS: This study included 10 hemispheres in 10 patients who underwent combined revascularization surgery for adult MMD. Digital subtraction angiography was performed before and 3 months after surgery, and selective iaCTA was performed from the ICA, ECA, and vertebral artery (VA) at the same times in a hybrid CT/digital subtraction angiography suite. The anatomical distribution of each vessel was determined and perfusion volume was measured quantitatively on contrast-enhanced axial CT images. RESULTS: Selective iaCTA clearly depicted the anatomical distribution of perfusion for each vessel. Conversion of blood supply from the ICA and VA to the ECA system was observed in the cerebral cortices and insulae but not in the basal ganglia. The mean volume of perfusion territories of the ECA (preoperative 0.9 cm3, postoperative 98.8 cm3); ICA (preoperative 225.7 cm3, postoperative 159.3 cm3); and VA (preoperative 244.0 cm3, postoperative 163.6 cm3) in the cerebral hemispheres changed significantly after revascularization. There was a correlation between increase in the ECA territory volume and decrease in the VA territory volume due to revascularization (R = -0.84, p < 0.005). CONCLUSIONS: Selective iaCTA enabled clear visualization of anatomical changes in each vascular perfusion territory and quantitative measurement of each perfusion volume. Perfusion conversion to the ECA system after bypass surgery was observed in the cortical regions and in the insulae on the bypass operation sides, but not in the basal ganglia. Combined revascularization promoted the development of ECA-perfused territory, which correlated with a decrease in hemodynamic burden of the posterior cerebral artery.

Blood Blister-Like Aneurysms at the Junction of the Internal Carotid and Posterior Communicating Artery: Characteristics and Treatment Strategies.

BACKGROUND: Blood blister-like aneurysms (BBAs) usually arise from the anterior walls of the internal carotid artery, and such lesions at the junction of the internal carotid artery and posterior communicating artery (PCoA) have not been reported to date. Here, we report our experiences of BBAs at PCoA. We studied their clinical and angiographical characteristics including the internal carotid-PCoA angle, an indicator of hemodynamic stress at the bifurcation. METHODS: Three patients with BBAs located at the origin of PCoA were studied. Wrap-clipping was adopted as the first-line therapy, but direct clipping was conducted when difficult. RESULTS: All patients were elderly females (mean age 81.3 years), and BBAs were small in size (mean maximum diameter 1.5 mm), which arose at the origins of wide-angled fetal-type PCoAs (mean internal carotid-PCoA angle 37.8 degrees). All the lesions were treated by surgery (direct clipping 2, wrap-clipping 1), and severe atherosclerotic changes were observed at adjacent arterial walls in all cases. Ordinary wrap-clipping using a polytetrafluoroethylene membrane via the transsylvian approach was difficult because of the limited working space, requiring some special techniques such as usage of fenestrated clips, polyglycolic acid sheets, and combined approach with subtemporal craniotomy. Good clinical outcomes were achieved in 2 patients. CONCLUSION: BBAs at PCoA were predominantly occurred as the small bulges at the origins of wide-angled fetal-type PCoAs in elderly females. Hemodynamic stress and atherosclerosis would contribute to the aneurysmal formation. Wrap-clipping or direct clipping with additional techniques would be useful for this rare condition.

Neuronal dysfunction and hemodynamic disturbance due to venous congestion in dural arteriovenous fistula revealed by 123I-iomazenil SPECT.

OBJECTIVE: Retrograde leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is associated with neurological morbidity and unfavorable outcomes. However, the direct damage to cortical neurons by dAVF with RLVD has not been elucidated. 123I-iomazenil (123I-IMZ) SPECT can reveal cerebral blood flow and cortical neuronal damage in early and late images, respectively. This study aimed to assess the cerebral venous congestive encephalopathy caused by dAVF using 123I-IMZ SPECT. METHODS: Based on the pre- and posttreatment MRI findings, patients were divided into three groups: a normal group, an edema group, and an infarction group. Radioactive counts in the early and late images of 123I-IMZ SPECT were investigated using the affected-to-contralateral side asymmetry ratio (ACR). RESULTS: None of the patients in the normal group showed any symptoms related to venous congestion. In contrast, all the patients in the edema and infarction groups developed neurological symptoms. The ACR in early images in the edema group was significantly lower than that in the normal group and significantly higher than that in the infarction group. The ACR in the late images of the infarction group was significantly lower than those of the normal and edema groups. After treatment, the neurological signs disappeared in the edema group, but only partial improvement was observed in the infarction group. The ACR in early images significantly improved after treatment in the edema group, but the ACR in late images did not change in any groups. CONCLUSIONS: 123I-IMZ SPECT is useful for evaluating hemodynamic disturbances and neuronal damage in dAVFs. The reduction in early images was correlated with the severity of venous congestive encephalopathy, and the significant reduction in late images is a reliable indicator of irreversible venous infarction caused by RLVD.

Recurring cervical internal carotid artery vasospasm elicited by head rotation: illustrative case.

BACKGROUND: Idiopathic extracranial internal carotid artery vasospasm (IEICAV) is a rare cerebrovascular disorder causing transient or permanent cerebral ischemia. The pathophysiology underlying this disorder is not well understood. Although various medical treatments have been tried, complete remission of vasospasm is difficult to achieve. The first case of bilateral IEICAV induced by head rotation, which was successfully treated by carotid artery stenting (CAS), was presented. OBSERVATIONS: A 40-year-old woman with bilateral IEICAV had been conservatively treated for 13 years. However, transient ischemic attacks (TIAs) were not suppressed. She eventually presented with a large brain infarction in the left hemisphere and was referred to our department. Digital subtraction angiography clearly demonstrated the triggering of internal carotid artery (ICA) vasospasm by head rotation. After CAS treatment, the TIAs disappeared completely. LESSONS: Clinicians should recognize that ordinary mechanical stimulation to the ICA by head rotation can induce vasospasm, and CAS should be performed for refractory IEICAV at the appropriate time to avoid cerebral infarction causing severe neurological deficits.

Hypoglossal canal dural arteriovenous fistula embolized under precise anatomical evaluation by selective intra-arterial injection computed tomography angiography.

Dural arteriovenous fistula (DAVF) involving the hypoglossal canal is rare but increasingly reported. To achieve complete obliteration without a procedure-related complication, understanding of the precise anatomy of this DAVF is essential. Here, we describe a 72-year-old man who underwent selective intra-arterial injection computed tomography angiography which allowed us to understand the detailed anatomy of the complex DAVF regarding access routes and the target regions for transvenous embolization (TVE). With the aid of this novel neuroimaging technique successful target TVE was achieved safely and completely.