Association of Genetic Variants with Postoperative Donor Artery Development in Moyamoya Disease: RNF213 and Other Moyamoya Angiopathy-Related Gene Analysis.

Robust postoperative bypass development is a characteristic of moyamoya disease (MMD); however, genetic factors mediating this phenomenon remain incompletely understood. Therefore, we aimed to elucidate the relationship between postoperative donor artery development and genetic variants. We retrospectively enrolled 63 patients (79 hemispheres) who underwent combined revascularization surgery. Postoperative development of the superficial temporal artery (STA), middle meningeal artery, and deep temporal artery (DTA) was assessed using the caliber-change ratio determined from magnetic resonance angiography measurements. We analyzed RNF213 and 36 other moyamoya angiopathy-related genes by whole-exome sequencing and extracted rare or damaging variants. Thirty-five participants carried RNF213 p.Arg4810Lys (all heterozygotes), whereas 5 had RNF213 rare variants (RVs). p.Arg4810Lys was significantly associated with postoperative DTA development, while age at surgery, hypertension, and hyperlipidemia were inversely associated. Multiple regression analysis revealed that age and p.Arg4810Lys held statistical significance (P = 0.044, coefficient - 0.015, 95% confidence interval (CI) - 0.029 to 0.000 and P = 0.001, coefficient 0.670, 95% CI 0.269 to 1.072, respectively). Those with RNF213 RV without p.Arg4810Lys exhibited a significant trend toward poor DTA development (P = 0.001). Hypertension demonstrated a significant positive association with STA development, which remained significant even after multiple regression analysis (P = 0.001, coefficient 0.303, 95% CI 0.123 to 0.482). Following Bonferroni correction for multiple comparisons, targeted analyses of RNF213 and 36 moyamoya angiopathy-related genes showed a significant association of only RNF213 p.Arg4810Lys with favorable DTA development (P = 0.001). A comprehensive analysis of RNF213, considering both p.Arg4810Lys and RVs, may provide a clearer prediction of postoperative DTA development.

Bypass-Assisted Microsurgical Clipping for an Endovascular Treatment-Resistant Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm, Recurring Two Decades Postinitial Clipping: 2-Dimensional Operative Video.

Salvage treatment of postclipping recurrent aneurysms remains challenging.1,2 The salvage microsurgical clipping is a possible intervention but sometimes difficult because of tissue adhesions around the aneurysm and previously installed clips; therefore, salvage coil embolization may have certain advantages.1-5 However, when coil embolization is not applicable,6 microsurgical clipping is a stand-alone curative treatment, requiring proficient and reliable microsurgical techniques. This article describes a unique case of a 70-year-old female patient complaining of a severe headache with subarachnoid hemorrhage due to a recurrent ruptured left internal carotid-posterior communicating artery aneurysm after microsurgical clipping 23 years ago. An initial attempt at coil embolization proved unsuccessful because of the aneurysm shape. Consequently, the salvage microsurgical clipping was planned. Given the additional time for trapping the internal carotid artery for the old clip removal, a superficial temporal artery-middle cerebral artery bypass was also planned. The operation entailed a superficial temporal artery-middle cerebral artery bypass, a Sylvian fissure dissection, the old clip removal, and aneurysm clipping. Intraoperatively, the complete aneurysm neck clipping was successfully performed without any complication, and patient postoperative course was uneventful. A wide surgical field should be obtained to be able to manipulate the aneurysm and old clip safely under a microscope. It is also important to temporarily trap the main artery to ensure removal of old clips and to prepare for intraprocedural ischemia using bypass after a precise assessment of hemodynamics before surgery. The patient provided informed consent for the procedure and the publication of the case along with its pertinent imaging, and this report was approved by the institutional review board at our hospital.

Orbital Arteriovenous Fistula Causing Only Visual Impairment due to Compression of the Optic Nerve by the Dilated Superior Ophthalmic Vein.

Orbital arteriovenous fistula (AVF) is a rare disease, and its standard therapeutic strategy has not been established. A 70-year-old male consulted an ophthalmologist due to a visual field defect in his left eye. Neurological findings showed visual impairment but no symptoms such as exophthalmos, conjunctival congestion, or diplopia. Magnetic resonance imaging showed marked dilation of the left superior ophthalmic vein (SOV). Cerebral angiography revealed an AVF that was limited to the left orbit. The feeder was a branch of the ophthalmic artery that originated from the first portion, and the drainer was the SOV, which was meandering and significantly dilated. Since the only symptom was visual impairment, the etiology was considered to be compression of the optic nerve due to a dilated SOV rather than increased venous pressure. Transvenous embolization via the facial vein was performed, and a visual field examination 1 week after the operation revealed marked improvement. Orbital AVF that develops only with visual impairment is extremely rare. As demonstrated with this case, coil embolization for proper position and reduction of the venous pressure, which relieves compression on the optic nerve, may be useful in improving the visual impairment.

RNF213 p.Arg4810Lys Wild Type is Associated with De Novo Hemorrhage in Asymptomatic Hemispheres with Moyamoya Disease.

Clinical implications of RNF213 genetic variants, other than p.Arg4810Lys, in moyamoya disease (MMD), remain unclear. This study aimed to investigate the association of RNF213 variants with clinical phenotypes in MMD. This retrospective cohort study collected data regarding the clinical characteristics of 139 patients with MMD and evaluated the angioarchitectures of 253 hemispheres using digital subtraction angiography at diagnosis. All RNF213 exons were sequenced, and the associations of clinical characteristics and angiographical findings with p.Arg4810Lys, p.Ala4399Thr, and other rare variants (RVs) were examined. Among 139 patients, 100 (71.9%) had p.Arg4810Lys heterozygote (GA) and 39 (28.1%) had the wild type (GG). Fourteen RVs were identified and detetcted in 15/139 (10.8%) patients, and p.Ala4399Thr was detected in 17/139 (12.2%) patients. Hemispheres with GG and p.Ala4399Thr presented with significantly less ischemic events and more hemorrhagic events at diagnosis (p = 0.001 and p = 0.028, respectively). In asymptomatic hemispheres, those with GG were more susceptible to de novo hemorrhage than those with GA (adjusted hazard ratio [aHR] 5.36) with an increased risk when accompanied by p.Ala4399Thr or RVs (aHR 15.22 and 16.60, respectively). Within the choroidal anastomosis-positive hemispheres, GG exhibited a higher incidence of de novo hemorrhage than GA (p = 0.004). The GG of p. Arg4810Lys was a risk factor for de novo hemorrhage in asymptomatic MMD hemispheres. This risk increased with certain other variants and is observed in choroidal anastomosis-positive hemispheres. A comprehensive evaluation of RNF213 variants and angioarchitectures is essential for predicting the phenotype of asymptomatic hemispheres in MMD.

Synthesis of Multiblock Copolymer Composed of Biodegradable Poly(butylene succinate) and Poly(2-pyrrolidone): Impact of Each Block Length on the Mechanical Properties.

A series of multiblock copolymers comprising a systematic combination of biomass-originated and biodegradable poly(butylene succinate) (PBS) and poly(2-pyrrolidone) (PA4) units is synthesized with various mean degrees of polymerization (mDP) of each unit. Despite the inherent immiscibility of PBS and PA4, multiblock structure allows to mix the two components in the solution-cast films from solution. The mechanical properties of the cast films are highly dependent on the mDP of each unit, as demonstrated by tensile tests. The film of the copolymer with the lowest mDP of each unit (PBS: 17, PA4: 10) is transparent and exhibits extremely high elongation at break (> 400%) and high tensile stress (39.5 MPa) with strain hardening. The films with 50% or higher crystallinity are brittle and opaque, while a decrease in crystallinity can result in higher elongation, as revealed by wide-angle X-ray diffraction measurements.

Clinical and Genetic Characteristics of Patients with Moyamoya Disease who Experienced Both Ischemic and Hemorrhagic Events.

OBJECTIVE: Cerebrovascular events in moyamoya disease are mainly classified into ischemic or hemorrhagic onset. It is rare for one patient to develop both ischemia and hemorrhage in moyamoya disease; detailed clinical course and genetic characteristics of such patients have not been elucidated. We aimed to clarify the clinical features of patients with both ischemic and hemorrhagic cerebrovascular events. METHODS: We analyzed the background factors, radiological features, and genotype of ring finger protein 213 c.14429 G > A (p.Arg4810Lys) of patients with moyamoya disease who visited our hospital between 1996 and 2020, and experienced both ischemic and hemorrhagic cerebrovascular events. Additionally, we analyzed factors that caused subsequent hemorrhage in adult-onset ischemic moyamoya disease. RESULTS: Of 262 patients, 12 presented with both ischemia and hemorrhage, of which, 4 exhibited pediatric onset and 8 had adult onset. In pediatric-onset subjects, ischemia was the initial event in all cases. Hemorrhagic events occurred at a median of 24.7 years postoperatively in patients who had undergone bypass surgery. In adult-onset subjects, ischemia preceded hemorrhage in 7 patients. In males, the interval to subsequent hemorrhage was significantly shorter for adult-onset ischemic moyamoya disease, and the hazard ratio for hemorrhagic events was 5.45. The ring finger protein 213 p.Arg4810Lys heterozygous variant was present in 9 patients. CONCLUSIONS: A majority of patients with moyamoya disease with both ischemia and hemorrhage experience an ischemic event first. Patients who developed ischemia in childhood may develop subsequent hemorrhage in approximately 20-25 years after bypass surgery. Male sex is a risk factor for a subsequent hemorrhagic event in adult-onset ischemic moyamoya disease.

Genetics of brain arteriovenous malformations and cerebral cavernous malformations.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

Genome-Wide Association Study of Intracranial Artery Stenosis Followed by Phenome-Wide Association Study.

The genetic background of intracranial artery stenosis (ICAS), a major cause of ischemic stroke, remains elusive. We performed the world's first genome-wide association study (GWAS) of ICAS using DNA samples from Japanese subjects, to identify the genetic factors associated with ICAS and their correlation with clinical features. We also conducted a phenome-wide association study (PheWAS) of the top variant identified via GWAS to determine its association with systemic disease. The GWAS involved 408 patients with ICAS and 349 healthy controls and utilized an Asian Screening Array of venous blood samples. The PheWAS was performed using genotypic and phenotypic data of the Biobank Japan Project, which contained information on 46 diseases and 60 quantitative trait data from > 150,000 Japanese individuals. The GWAS revealed that the East Asian-specific functional variant of RNF213, rs112735431 (c.14429G > A, p.Arg4810Lys), was associated with ICAS (odds ratio, 12.3; 95% CI 5.5 to 27.5; P = 7.8 × 10-10). Stratified analysis within ICAS cases demonstrated that clinical features of those with and without the risk allele were different. PheWAS indicated that high blood pressure and angina were significantly associated with RNF213 rs112735431. The first GWAS of ICAS, which stratifies subpopulations within the ICAS cases with distinct clinical features, revealed that RNF213 rs112735431 was the most significant variant associated with ICAS. Thus, RNF213 rs112735431 shows potential as an important clinical biomarker that characterizes pleiotropic risk in various vascular diseases, such as blood pressure and angina, thereby facilitating personalized medicine for systemic vascular diseases in East Asian populations.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.

Extradural Middle Fossa and Transcavernous Approach for Resection of Trigeminal Neurinoma at Lateral Cavernous Sinus.

We present a 52-year-old male case of right trigeminal neurinoma at lateral cavernous sinus. The tumor was 40 mm in maximum diameter, obviously compressed temporal lobe and encased internal carotid artery. Extradural middle fossa and transcavernous approach was applied and the tumor was resected via Parkinson's triangle. This approach enabled safe and effective tumor resection, sufficient visualization, and operative field ( Figs. 1 and 2 ). We performed dissection of the tumor from trigeminal nerve, tentorium, and middle fossa and resect the tumor around internal carotid artery sufficiently. Postoperative course was good without any new neurological deficit. This surgical method is considered safe and effective for the resection of the tumor at lateral cavernous sinus. The link to the video can be found at: https://youtu.be/2ekuILIgEuo.

STA-A3 Bypass Using Radial Artery Graft for Progressive Cerebral Infarction of Bilateral ACA Region after STA-MCA Bypass Surgery for Moyamoya Disease.

Direct revascularization surgery, such as superficial temporal artery (STA)-middle cerebral artery (MCA) bypass, is effective in preventing ischemia and hemorrhage for moyamoya disease. On the other hand, when ischemia of the anterior cerebral artery (ACA) region progresses after ipsilateral STA-MCA bypass, it is difficult to perform revascularization from the viewpoint of the donor artery. A 55-year-old woman with right hemiparesis was diagnosed with cerebral infarction due to moyamoya disease. Left STA-MCA bypass was performed with no postoperative complications, but memory impairment and decreased motivation were observed 2 months after the operation. Magnetic resonance imaging and angiography revealed new infarction in the bilateral ACA area and deterioration in the signal intensity of bilateral ACAs. Revascularization of the bilateral ACA regions was considered necessary, but the left STA was already used in the previous surgery. Therefore, STA-radial artery (RA)-A3 bypass using RA graft combined with right STA-MCA bypass was performed. STA-A3 bypass using an RA graft may be the optimal treatment for ischemia of the ACA region that progresses after STA-MCA bypass.

[Superficial Temporal Artery:Middle Cerebral Artery Bypass Technique as the Basis for Emergency Revascularization].

The superficial temporal artery-middle cerebral artery(STA-MCA)bypass technique is extremely important as the basis for both cerebral revascularization in chronic-stage ischemia and emergency surgical revascularization, including open surgical embolectomy. The sophisticated technique of microvascular bypass could also contribute to rescuing inadvertent vascular injuries, such as those occurring in difficult tumor surgery. Therefore, novice neurosurgeons should practice mastering the microvascular suturing technique.

Stimulation of brain corticotropin-releasing factor receptor type1 facilitates the rat micturition via brain glutamatergic receptors.

Corticotropin-releasing factor (CRF), a representative stress-related neuropeptide, in the central nervous system reportedly both facilitates and suppresses the micturition, therefore, roles of central CRF in regulation of the micturition are still controversial. In this study, we investigated (1) effects of intracerebroventricularly (icv)-administered CRF on the micturition, and (2) brain CRF receptor subtypes (CRFR1/CRFR2) and glutamatergic receptors (NMDA/AMPA subtypes) involved in the CRF-induced effects in male Wistar rats under urethane anesthesia. Intercontraction intervals (ICI), and maximal voiding pressure (MVP), were evaluated by continuous cystometry 45 min before CRF administration or intracerebroventricular pretreatment with other drugs as follows and 3 h after CRF administration. Single-voided volume (Vv), post-voiding residual volume (Rv), bladder capacity (BC), and voiding efficiency (VE) were evaluated by single cystometry 60 min before CRF administration and 60-120 min after the administration. Icv-administered CRF reduced ICI, Vv, and BC without changing MVP, Rv, or VE. The CRF-induced ICI reduction was attenuated by icv-pretreated CP154526 (CRFR1 antagonist), MK-801 (NMDA receptor antagonist), and DNQX (AMPA receptor antagonist), but not by K41498 (CRFR2 antagonist). These results indicate that stimulation of brain CRFR1 can be involved in facilitation of the rat micturition via brain NMDA/AMPA receptors.

RNF213 p.Arg4810Lys Heterozygosity in Moyamoya Disease Indicates Early Onset and Bilateral Cerebrovascular Events.

The relationship between RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variants and clinical manifestation in patients with Moyamoya disease (MMD) remains unclear. We performed a retrospective cohort analysis to clarify the genotype-phenotype correlation of this RNF213 hotspot variant in MMD patients, especially between wild-type (GG) and heterozygous (GA) genotypes. Clinical and genetic data were obtained from patients diagnosed with MMD in our institutions between October 2011 and November 2020. Clinical data included age, sex, neurological status at diagnosis, medical history, smoking history, alcohol intake, and family history. Of the 225 enrolled patients, 160 (71.1%) were symptomatic, 3 (1.3%) had the homozygous variant, and 149 (66.2%) had the heterozygous variant (GA). Analysis of all enrolled patients showed that the GA group was prone to present bilateral symptoms (p = 0.008) and progressive status (Suzuki grade ≥ 4; p = 0.017). Analysis limited to symptomatic patients revealed that the GA group had bilateral symptoms (p = 0.017), younger age at onset (p = 0.043), and, in particular, a higher proportion of onset before 25 years of age (p = 0.021). Multivariate logistic regression analysis of overall patients revealed that earlier age at diagnosis (p < 0.001, OR 0.936, 95% CI 0.914-0.959) and GA group (p = 0.017, OR 3.326, 95%CI 1.237-8.941) were significantly associated with bilateral symptoms. MMD patients diagnosed at a young age with the RNF213 heterozygous variant should be followed up with consideration of possible contralateral stroke if one hemisphere is already symptomatic or of early cerebrovascular events if bilateral hemispheres are asymptomatic.

T11/T12 ossification of the yellow ligament contributing to thoracic myelopathy in patient with posterior fossa arachnoid cyst and acquired incidental Chiari I malformation/syrinx.

BACKGROUND: Thoracic ossification of the yellow ligament (OYL) may contribute to myelopathy. In the case presented, the patient additionally had a chronic posterior fossa arachnoid cyst with an acquired Chiari I malformation and cervicothoracic syrinx. CASE DESCRIPTION: A 40-year-old female with a posterior fossa arachnoid cyst found 17 years ago, and newly acquired Chiari I malformation (tonsils down 5 mm) with a C7-T5 syrnix, presented with the new onset of lower extremity myelopathy. The MR documented marked dorsolateral cord compression due to T11/T12 OYL. Six months following a laminectomy for resection of OYL, the patient was asymptomatic. CONCLUSION: In patients presenting with the new onset of lower extremity myelopathy, evaluation of the complete neuraxis may be warranted. Here, the patient has an unchanged posterior fossa arachnoid cyst with an acquired Chiari I malformation/C7-T5 syrinx. However, the patient's symptoms were fully attributed to the MR-documented T11/T12 OYL that was successfully resected.

Differences in Clinical Features among Different Onset Patterns in Moyamoya Disease.

Moyamoya disease is characterized by severe stenosis at the ends of the bilateral internal carotid arteries and the development of collateral circulation. The disease is very diverse in terms of age at onset, onset patterns, radiological findings, and genetic phenotypes. The pattern of onset is mainly divided into ischemic and hemorrhagic onsets. Recently, the opportunity to identify asymptomatic moyamoya disease, which sometimes manifests as nonspecific symptoms such as headache and dizziness, through screening with magnetic resonance imaging has been increasing. Various recent reports have investigated the associations between the clinical features of different onset patterns of moyamoya disease and the corresponding imaging characteristics. In this article, we have reviewed the natural history, clinical features, and imaging features of each onset pattern of moyamoya disease.

Impact of Extracranial-Intracranial Bypass on Cognitive Function in a Patient with Chronic Cerebral Ischemia.

Extracranial-intracranial (EC-IC) arterial bypass surgery was developed to prevent subsequent stroke by improving hemodynamics distal to the occluded intracranial artery, but its utilization has been decreasing due to the development in medical treatment. However, EC-IC bypass surgery may be effective for arresting or reversing cognitive decline in patients with cerebral ischemia. A 69-year-old man with the left internal carotid artery occlusion that manifested as scattered cerebral infarction of the left hemisphere presented with dysarthria and transient right hemiparesis. Hemodynamic condition was impaired in the left side, and therefore, EC-IC bypass surgery was performed to prevent recurrence of cerebral infarction. Neuropsychological examination at 6 months after the surgery showed marked improvement as compared to the preoperative examination and there was no recurrence of stroke in the patient. EC-IC bypass may contribute to the improvement of cognitive function as well as the prevention of recurrence of cerebral infarction in patients with hemodynamic insufficiency, but there might be a threshold of hemodynamic impairment with respect to the reversibility of cognitive performance. Investigation of the target and timing can identify cases in which the cognitive function is improved by surgery.

Neuroendovascular Training Using Multisource Video-Recording System in a Hybrid Operating Room.

BACKGROUND: Increasing restrictions over trainees' working hours and the recent coronavirus disease 2019 pandemic warrant new educational methods of surgical skills. We assessed a novel video-recording system for neuroendovascular skill education, developed with the installation of a hybrid operating room (OR) at our institution. METHODS: A single-plane angiography unit with a large flat display (FlexVision XL; Philips Medical Systems) was installed in our OR. All media sources in the OR, including live fluoroscopy and ceiling-mounted camcorders, were connected to a video switcher. This video switcher laid up to 8 video images into one big image, which was transferred to the large display and the professional-use Blu-ray recorder. The recording was performed continuously during the procedure. This recording system was evaluated retrospectively with a questionnaire administered to the 5 trainees. RESULTS: Using this system, 68 interventional procedures were recorded. Among the potential merits, the trainees assigned the greatest value to the simultaneous recording of the operator's hand motions and the fluoroscopy images. Among the potential limitations of the system, the prolonged time and the increased volume of the video data bothered the trainees the most. The recorded video looked like a live demonstration. CONCLUSIONS: Our "selfie" video recording system was useful for skill training of neuroendovascular interventions.

Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors.

Brain nicotinic acetylcholine receptors (nAChRs) reportedly suppress the micturition, but the mechanisms responsible for this suppression remain unclear. We previously reported that intracerebroventricularly administered (±)-epibatidine (non-selective nAChR agonist) activated the sympatho-adrenomedullary system, which can affect the micturition. Therefore, we investigated (1) whether intracerebroventricularly administered (±)-epibatidine-induced effects on the micturition were dependent on the sympatho-adrenomedullary system, and (2) brain nAChR subtypes involved in the (±)-epibatidine-induced effects in urethane-anesthetized male Wistar rats. Plasma noradrenaline and adrenaline (catecholamines) were measured just before and 5 min after (±)-epibatidine administration. Evaluation of urodynamic parameters, intercontraction intervals (ICI) and maximal voiding pressure (MVP) by cystometry was started 1 h before (±)-epibatidine administration or intracerebroventricular pretreatment with other drugs and continued 1 h after (±)-epibatidine administration. Intracerebroventricularly administered (±)-epibatidine elevated plasma catecholamines and prolonged ICI without affecting MVP, and these changes were suppressed by intracerebroventricularly pretreated mecamylamine (non-selective nAChR antagonist). Acute bilateral adrenalectomy abolished the (±)-epibatidine-induced elevation of plasma catecholamines, but had no effect on the (±)-epibatidine-induced ICI prolongation. The latter was suppressed by intracerebroventricularly pretreated methyllycaconitine (selective α7-nAChR antagonist), SR95531 (GABAA antagonist), and SCH50911 (GABAB antagonist), but not by dihydro-ß-erythroidine (selective α4ß2-nAChR antagonist). Intracerebroventricularly administered PHA568487 (selective α7-nAChR agonist) prolonged ICI without affecting MVP, similar to (±)-epibatidine. These results suggest that stimulation of brain α7-nAChRs suppresses the rat micturition through brain GABAA/GABAB receptors, independently of the sympatho-adrenomedullary outflow modulation.