Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143-/y ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143-/y mice. The phenotypic defect in Gpr143-/y mice was mimicked in cholinergic interneuron-specific Gpr143-/y (Chat-cre;Gpr143flox/y ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser240/244 in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143flox/y mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143flox/y mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs.

Endoscopic Evacuation of Putaminal Hemorrhage Using the Trans-Middle Temporal Gyrus Approach: Technical Notes and Case Presentations.

BACKGROUND: The development of minimally invasive endoscopic neurosurgery has enabled widespread application of endoscopic surgery via the ipsilateral transfrontal approach for putaminal hematoma evacuation. However, this approach is unsuitable for putaminal hematomas that extend into the temporal lobe. We adopted the endoscopic trans-middle temporal gyrus approach, instead of the conventional surgical approach, for the management of these complicated cases and determined its safety and feasibility. METHODS: Twenty patients with putaminal hemorrhage underwent surgical treatment at the Shinshu University Hospital between January 2016 and May 2021. Of these, two patients with left putaminal hemorrhage that extended into the temporal lobe underwent surgical treatment using the endoscopic trans-middle temporal gyrus approach. The procedure entailed the use of a thinner transparent sheath to reduce the technique's invasiveness, a navigation system to determine the location of the middle temporal gyrus and the sheath's trajectory, and an endoscope with a 4K camera for higher image quality and utility. The sylvian fissure was compressed superiorly using our novel "port retraction technique" (i.e., by tilting the transparent sheath superiorly) to avoid damage to the middle cerebral artery and Wernicke's area. RESULTS: The endoscopic trans-middle temporal gyrus approach allowed sufficient hematoma evacuation and hemostasis under endoscopic observation without any surgical complexities or complications. The postoperative course was uneventful in both patients. CONCLUSION: The endoscopic trans-middle temporal gyrus approach for putaminal hematoma evacuation helps avoid damage to normal brain tissue, which could result from the wide range of motion of the conventional technique, particularly when the hemorrhage extends to the temporal lobe.

A new very-small-bore Simmons guiding sheath for transradial neurointervention: Technical note and initial experience.

Transradial access during neurointerventions has increased in popularity because of reduced complications and patient preference. Nevertheless, transradial cannulation into the left common carotid artery can be difficult technically because of the lack of catheter support in the aortic arch. Furthermore, the use of large sheaths can increase the risk of complications at the access site. Here, we developed a new very-small-bore transradial system using a 3F Simmons guiding sheath, to increase the procedural success rate and minimize access-site complications. This system can represent a valuable treatment option for neurointerventions and has the potential to expand the indications for transradial access.

Smaller diameter sheaths are required to safely perform transradial neurointerventions.

We read with great interest the paper titled "Transradial access with Simmons guiding catheter for carotid artery stenting: Feasibility and procedural complications in a single-center experience" by Muszynski et al. The authors concluded that a transradial carotid artery stenting (CAS) using a Glidesheath Slender 7F Introducer/7F Envoy Simmons 2 catheter system was feasible with a high procedural success rate and low access site complication rate. We completely agree with their conclusions. In this study, large-diameter sheaths were used. Large sheaths increase the risk of developing radial artery spasms. Interventionalists must be aware that radial artery spasm can not only require an access crossover, but can also cause severe access site complications, such as eversion or avulsion of the radial artery, catheter/sheath entrapment, and compartment syndrome. A 6F Simmons guiding sheath has a smaller outer diameter than the Glidesheath Slender 7F Introducer does, and it offers a large-bore working channel compatible with a 10-mm diameter Wallstent and Acculink. Transradial CAS with a 6F Simmons guiding sheath has previously yielded a high procedural success rate without serious access site complications. Nevertheless, we believe that a further decrease in the sheath diameter is required to safely perform transradial neurointerventions in more patients.

Lethal and mutagenic effects of different LET radiations on Bacillus subtilis spores.

New, useful microorganism resources have been generated by ionizing radiation breeding technology. However, the mutagenic effects of ionizing radiation on microorganisms have not been systematically clarified. For a deeper understanding and characterization of ionizing radiation-induced mutations in microorganisms, we investigated the lethal effects of seven different linear energy transfer (LET) radiations based on the survival fraction (SF) and whole-genome sequencing analysis of the mutagenic effects of a dose resulting in an SF of around 1% in Bacillus subtilis spores. Consequently, the lower LET radiations (gamma [surface LET: 0.2 keV/µm] and 4He2+ [24 keV/µm]) showed low lethality and high mutation frequency (MF), resulting in the major induction of single-base substitutions. Whereas higher LET radiations (12C5+ [156 keV/µm] and 12C6+ [179 keV/µm]) showed high lethality and low MF, resulting in the preferential induction of deletion mutations. In addition, 12C6+ (111) ion beams likely possess characteristics of both low- and high-LET radiations simultaneously. A decrease in the relative biological effectiveness and an evaluation of the inactivation cross section indicated that 20Ne8+ (468 keV/µm) and 40Ar13+ (2214 keV/µm) ion beams had overkill effects. In conclusion, in the mutation breeding of microorganisms, it should be possible to regulate the proportions, types, and frequencies of induced mutations by selecting an ionizing radiation of an appropriate LET in accordance with the intended purpose.

Left Transradial Access Using a Radial-Specific Neurointerventional Guiding Sheath for Coil Embolization of Anterior Circulation Aneurysm Associated With the Aberrant Right Subclavian Artery: Technical Note and Literature Review.

BACKGROUND: Aberrant right subclavian artery (ARSA) is a rare condition, but the most common anomaly of the aortic arch. Although neurointerventions via transradial access (TRA) are becoming increasingly popular worldwide, transradial carotid cannulation has been extremely challenging in patients with an ARSA. Herein, we present a case of ARSA-associated anterior communicating artery (ACoA) aneurysm that was successfully treated with a radial-specific 6F Simmons guiding sheath via left TRA. We also review the relevant literature. METHODS: A 68-year-old-woman who was diagnosed as having an ARSA-associated ACoA aneurysm underwent simple coiling via left TRA. After the 6F Simmons guiding sheath was engaged into the right common carotid artery using the pull-back-technique, transradial quadraxial system (6F Simmons guiding sheath/6F intermediate catheter/3.2F intermediate catheter/coil-delivery microcatheter) was implemented. RESULTS: Simple coiling of the aneurysm was successfully achieved without catheter kinking or system instability. The postprocedural course was uneventful. A follow-up magnetic resonance angiography showed no evidence of recanalization 1 years 9 months after the procedure. CONCLUSIONS: Transradial anterior circulation intervention has been rarely used for patients with an ARSA due to unfavorable catheter trajectory. Left TRA using the 6F Simmons guiding sheath is a useful treatment option to address anterior circulation interventions for patients with an ARSA. Preoperative diagnosis of ARSA is necessary for the application of our method.

The efficacy of a visiting surgical service versus that of a hospital-based surgical service in providing endoscopic endonasal surgery to remove nonfunctioning pituitary adenomas in rural communities.

PURPOSE: To satisfy the increasing demand for endoscopic endonasal approach (EEA) to treat pituitary tumors, especially in rural areas, the "mobile EEA" system, a visiting surgical service, has been established We report this unique system for maintaining community healthcare and evaluate the surgical results of mobile EEA. METHODS: A retrospectively acquired database of 225 consecutive cases of EEA at Shinshu University Hospital (i.e., "home EEA") and its affiliated hospitals (i.e., "away EEA") between May 2018 and May 2022 was reviewed. A total of 105 consecutive patients who fulfilled the criterion of a diagnosis of new-onset nonfunctioning pituitary adenoma (PA) were included. Clinical characteristics and postoperative clinical outcomes were statistically compared between the home EEA and away EEA groups to assess the presence of a home advantage and/or an away disadvantage. RESULTS: Patients were stratified into two cohorts: patients treated at our hospital (home EEA: n = 41 [39.0%]) and those treated in the visiting surgical service at an affiliated hospital (away EEA: n = 64 [61.0%]). Postoperative clinical outcomes, such as the extent of tumor resection (p = 0.39), operation time (p = 0.80), visual function (p = 0.54), and occurrence of surgical complications (p = 0.53), were comparable between the groups. There were no visiting surgical service-related adverse events or accidents caused by physicians' driving to away hospitals. CONCLUSION: Pituitary surgeries performed via the mobile EEA system for nonfunctioning PAs may help maintain local community healthcare. Furthermore, this system can also contribute to the efficient training of surgeons by the same experienced pituitary surgeon using the same protocol.

Surgical Trapping of a Cavernous Carotid Aneurysm Causing Carotid Cavernous Fistula After Flow Diverter Placement: Technical Note and Literature Review.

BACKGROUND: Flow diverter (FD) treatment is a promising therapeutic strategy for intracranial aneurysms such as cavernous carotid aneurysms (CCAs). Direct cavernous carotid fistula (CCF) caused by delayed rupture of FD-treated CCAs has been reported, and endovascular therapy has been used in the literature. Surgical treatment is warranted for patients who have failed or are ineligible for endovascular treatment. However, no studies have evaluated surgical treatment to date. Here, this paper presents the first case of direct CCF due to delayed rupture of an FD-treated CCA managed with surgical internal carotid artery (ICA) trapping with bypass revascularization, in which the intracranial ICA with FD placement was successfully occluded with aneurysm clips. METHODS: A 63-year-old man with a diagnosis of large symptomatic left CCA underwent FD treatment. The FD was deployed from the supraclinoid segment of the ICA distal to the ophthalmic artery to the petrous segment of the ICA. Since angiography 7 months after the FD placement showed progressive direct CCF, left superficial temporal artery-middle cerebral artery bypass followed by ICA trapping was performed. RESULTS: The intracranial ICA proximal to the ophthalmic artery where the FD was placed was successfully occluded using two aneurysm clips. The postoperative course was uneventful. Follow-up angiography 8 months after the surgery confirmed complete obliteration of the direct CCF and CCA. CONCLUSIONS: The intracranial artery in which the FD was deployed was successfully occluded with two aneurysm clips. ICA trapping can be a feasible and useful therapeutic option to treat direct CCF caused by FD-treated CCAs.

Comparative analysis of seed and seedling irradiation with gamma rays and carbon ions for mutation induction in Arabidopsis.

The molecular nature of mutations induced by ionizing radiation and chemical mutagens in plants is becoming clearer owing to the availability of high-throughput DNA sequencing technology. However, few studies have compared the induced mutations between different radiation qualities and between different irradiated materials with the same analysis method. To compare mutation induction between dry-seeds and seedlings irradiated with carbon ions and gamma rays in Arabidopsis, in this study we detected the mutations induced by seedling irradiation with gamma rays and analyzed the data together with data previously obtained for the other irradiation treatments. Mutation frequency at the equivalent dose for survival reduction was higher with gamma rays than with carbon ions, and was higher with dry-seed irradiation than with seedling irradiation. Carbon ions induced a higher frequency of deletions (2-99 bp) than gamma rays in the case of dry-seed irradiation, but this difference was less evident in the case of seedling irradiation. This result supported the inference that dry-seed irradiation under a lower water content more clearly reflects the difference in radiation quality. However, the ratio of rearrangements (inversions, translocations, and deletions larger than 100 bp), which are considered to be derived from the rejoining of two distantly located DNA breaks, was significantly higher with carbon ions than gamma rays irrespective of the irradiated material. This finding suggested that high-linear energy transfer radiation induced closely located DNA damage, irrespective of the water content of the material, that could lead to the generation of rearrangements. Taken together, the results provide an overall picture of radiation-induced mutation in Arabidopsis and will be useful for selection of a suitable radiation treatment for mutagenesis.

Real-Time Monitoring of Aneurysm Catheterization During Stent-Assisted Coiling for Irregularly Shaped Intracranial Aneurysms: The Scope Technique.

OBJECTIVE: Stent-assisted coiling (SAC) using the jailing technique is a well-established treatment for wide-neck intracranial aneurysms. However, low-volume packing, which is a key factor for aneurysm recanalization, can occur in patients with irregularly shaped aneurysms. We have devised a real-time monitoring system for aneurysm catheterization that allows the intentional placement of the jailed coil-delivery microcatheter and deployed stent, referred to as the "scope" technique. Herein, we present a case of irregularly shaped anterior communicating artery (ACoA) aneurysm successfully treated with SAC using this technique. METHODS: A 72-year-old woman diagnosed with an unruptured wide-neck ACoA aneurysm that was eccentric to the parent ACoA and overhanging posteriorly underwent SAC using this technique. Bilateral transradial quadraxial systems (6-Fr Simmons guiding sheath/6-Fr intermediate catheter/3.2-Fr intermediate catheter/microcatheter) were established via right and left internal carotid artery. The stent-delivery microcatheter was advanced into the left A2 via the right A1, leaving a 0.014″ microguidewire for visualization under fluoroscopic guidance. To place the coil-delivery microcatheter in the middle of the aneurysm after stent deployment, the coil-delivery microcatheter was cannulated into the aneurysm via the left A1, intendedly through the posterior side of the stent-delivery microcatheter in the down-the-barrel view of the parent ACoA (the scope technique). RESULTS: After stent deployment, SAC of the aneurysm was successfully achieved. CONCLUSIONS: Using this technique, the coil-delivery microcatheter was cannulated into the aneurysm, while monitoring its positional relationship with the stent-delivery microcatheter in real time. This technique is a useful treatment option for irregularly shaped and wide-neck aneurysms.

Coupling between GPR143 and dopamine D2 receptor is required for selective potentiation of dopamine D2 receptor function by L-3,4-dihydroxyphenylalanine in the dorsal striatum.

Dopamine (DA) is involved in neurological and physiological functions such as motor control. L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of DA, is conventionally believed to be an inert amino acid precursor of DA, and its major therapeutic effects in Parkinson's disease (PD) are mediated through its conversion to DA. On the contrary, accumulating evidence suggests that L-DOPA itself is a neurotransmitter. We here show that L-DOPA potentiates DA D2 receptor (DRD2) signaling through GPR143, the gene product of X-linked ocular albinism 1, a G-protein-coupled receptor for L-DOPA. In Gpr143-gene-deficient (Gpr143-/y ) mice, quinpirole, a DRD2/DRD3 agonist, -induced hypolocomotion was attenuated compared to wild-type (WT) mice. Administration of non-effective dose of L-DOPA methyl ester augmented the quinpirole-induced hypolocomotion in WT mice but not in Gpr143-/y mice. In cells co-expressing GPR143 and DRD2, L-DOPA enhanced the interaction between GPR143 and DRD2 and augmented quinpirole-induced decrease in cAMP levels. This augmentation by L-DOPA was not observed in cells co-expressing GPR143 and DRD1 or DRD3. Chimeric analysis in which the domain of GPR143 was replaced with GPR37 revealed that GPR143 interacted with DRD2 at the fifth transmembrane domain. Intracerebroventricular administration of a peptide that disrupted the interaction mitigated quinpirole-induced behavioral changes in WT mice but not in Gpr143-/y mice. These findings provide evidence that coupling between GPR143 and DRD2 is required for selective DRD2 modulation by L-DOPA in the dorsal striatum.

Transradial Mechanical Thrombectomy Using a Radial-specific Neurointerventional Guiding Sheath for Anterior Circulation Large-Vessel Occlusions: Preliminary Experience and Literature Review.

BACKGROUND: Transradial mechanical thrombectomy (MT) is increasingly used because it is associated with a low incidence of vascular access site complications. However, transradial carotid cannulation can be technically challenging to perform in patients with an unfavorable supra-aortic takeoff. In this study, the feasibility and safety of a new transradial MT system with a radial-specific neurointerventional guiding sheath-6F Simmons guiding sheath was evaluated-in patients with anterior circulation large-vessel occlusions. Additionally, a literature review was performed. METHODS: We retrospectively analyzed data from our institutional database about consecutive patients who underwent transradial MT for anterior circulation large-vessel occlusion. After the 6F Simmons guiding sheath was engaged into the target common carotid artery, a triaxial system (Simmons guiding sheath/aspiration catheter/microcatheter), was established. MT using the continuous aspiration prior to intracranial vascular embolectomy technique was performed. Then, procedural success rate, successful revascularization, and procedure-related complications were assessed. RESULTS: A total of 13 patients who had transradial MT were included in the analysis. All 13 patients underwent successful thrombectomy without catheter kinking or system instability, and 12 of them achieved successful revascularization (modified Thrombolysis in Cerebral Infarction score of ≥2b). No complications occurred. CONCLUSIONS: To the best of our knowledge, this is the first case series on transradial MT using a radial-specific neurointerventional system for anterior circulation large-vessel occlusions. This method may increase the success rate of transradial MT. Based on our initial experience, transradial MT, using this system, was feasible and safe for anterior circulation large-vessel occlusions.

Real-time angiography in endovascular revascularization of intracranial atherosclerotic internal carotid artery stenosis under proximal balloon protection: "Retrograde suction-injection" technique and literature review.

Intracranial angioplasty/stenting is a treatment option for patients with symptomatic intracranial atherosclerotic disease refractory to aggressive medical treatment. However, it carries a risk of procedure-related embolism as well as reperfusion hemorrhage and in-stent thrombosis. We have devised a new embolic protection system which can achieve both total ipsilateral internal carotid artery (ICA) embolic protection and real-time visualization of the target lesion during endovascular revascularization of intracranial atherosclerotic disease below the carotid T junction. Herein, we describe a case of medically refractory symptomatic intracranial atherosclerotic ICA stenosis successfully treated with this method.