A Relaxin-Like Gonad-Stimulating Peptide Appears in the Early Development of the Starfish Patiria pectinifera.

Relaxin-like gonad-stimulating peptide (RGP) is a hormone with gonadotropin-like activity in starfish. This study revealed that spawning inducing activity was detected in an extract of brachiolaria larvae of Patiria pectinifera. Spawning inducing activity in the extract was due to P. pectinifera RGP (PpeRGP), not 1-methyladenine. The expression of PpeRGP mRNA was also found in brachiolaria. Immunohistochemical observation with specific antibodies for PpeRGP showed that PpeRGP was distributed in the peripheral adhesive papilla of the brachiolaria arms. In contrast, PpeRGP was not detected in the adult rudiment or ciliary band regions, which are present in the neural system. These findings strongly suggest that RGP exists in the larvae before metamorphosis. Because gonads are not developed in starfish larvae, it seems likely that RGP plays another role other than gonadotropic action in the early development of starfish.

The Modifying of Functional Connectivity Induced by Peripheral Nerve Field Stimulation using Electroacupuncture for Migraine: A Prospective Clinical Study.

OBJECTIVE: We examined the functional connectivity (FC) in patients with migraine compared with healthy subjects before and after C2 peripheral nerve field stimulation with electroacupuncture (EA-C2-PNfS) to evaluate the effect of EA-C2-PNfS and elucidate the mechanism of migraine. METHODS: Twenty-six patients with migraine and 24 healthy controls were recruited. All patients underwent resting state functional magnetic resonance imaging before and after 3 months of EA-C2-PNfS. We evaluated a numerical rating scale, the Headache Impact Test, and the Self-Rating Depression Scale, which assesses depression. Healthy controls underwent magnetic resonance imaging twice at a 3-month interval without acupuncture. An analysis of FC in the region of interest in the pain matrix was performed. RESULTS: Twenty patients with migraine and 23 healthy controls (mean ± standard deviation: 44.9 ± 12.9 years of age) were included. Three patients had migraine with aura (55.0 ± 18.0 years of age), 11 patients had migraine without aura (MWoA) (45.6 ± 14.6 years of age), and six patients had chronic migraine (40.8 ± 13.9 years of age). The clinical assessments significantly improved after EA-C2-PNfS in the MWoA group only. In FC analysis, the MWoA group showed a significant decrease after EA-C2-PNfS in FC between the right hypothalamus and left insula. Right hypothalamus-related FC was lower before acupuncture in the chronic migraine group than in the MWoA group. CONCLUSION: After EA-C2-PNfS for MWoA, significant changes in FC were observed at the hypothalamus and insula. Our results indicate that EA-C2-PNfS could improve migraine headache by modifying pain-related FC.

Migraine Pathophysiology Revisited: Proposal of a New Molecular Theory of Migraine Pathophysiology and Headache Diagnostic Criteria.

Various explanations for the pathophysiology of migraines have been proposed; however, none of these provide a complete explanation. The author critically reviews previous theories and proposes a new molecular theory of migraine pathophysiology. The diagnosis of primary headaches is generally based on clinical histories and symptoms only because there is no reliable diagnostic examination. The author proposes a new classification system and set of diagnostic criteria for headaches based on molecular markers.

[Diagnosis and Therapy for Idiopathic Intracranial Hypertension].

Idiopathic intracranial hypertension is a pathological state of increased intracranial pressure without intracranial mass lesion, vascular lesion, or hydrocephalus. For the diagnosis of this pathology, various secondary and primary headaches, such as migraine and medication overuse headaches should be excluded. Radiological imaging, including diffusion tensor imaging may show secondary findings of intracranial hypertension. These imaging techniques may be useful to diagnose intracranial hypertension, because at present there is no reliable non-invasive method to measure intracranial pressure. The pathophysiology of idiopathic intracranial hypertension has not been revealed; however there are some theories include, the disorder of cerebrospinal fluid circulation, disturbance of intracranial venous circulation, and metabolic disorders. Headache, nausea, and optic disc edema are frequently observed. The disease is frequently seen in obese females of childbearing age. Several therapies, including weight reduction, medication, and surgery have been studied; however the level of evidence for these therapies remains low.

Clinical Effect of C2 Peripheral Nerve Field Stimulation Using Electroacupuncture for Primary Headache.

OBJECTIVE: We applied C2 peripheral nerve field stimulation using electroacupuncture (EA-C2-PNfS) for primary headache, and investigated its clinical effectiveness. MATERIALS AND METHODS: Fifty-four primary headache patients (10 men, 44 women) with a mean age of 48.6 ± 15.0 years underwent EA-C2-PNfS for three months. We used questionnaires to assess outcomes; pain intensity (11-point numerical rating scale [NRS]), quality of daily life (Headache Impact Test [HIT-6]), depression (Self-Rating Depression Scale [SDS]). Monthly headache days and acute headache medication days were obtained from diaries. RESULTS: The headache intensity significantly declined after the EA-C2-PNfS with reduction of NRS pain scale; 7.4 ± 1.9 at baseline, 4.9 ± 2.9 at three month (p < 0.001). Both HIT-6 and SDS showed significant improvement (p < 0.001). Some patients showed moderate depression in SDS before treatment, that was alleviated in patients with tension-type headache after the EA-C2-PNfS. Monthly headache days significantly decreased from 18.0 ± 9.0 at one month to 14.0 ± 10.2 at three months (p < 0.001), accompanied with reduction of the monthly acute headache medication days from 8.0 ± 6.7 to 6.4 ± 6.5 (p = 0.003). CONCLUSIONS: EA-C2-PNfS was successfully used for reducing severity and disability in primary headache patients. We conclude that EA-C2-PNfS is a favorable option for medically intractable primary headache as less-invasive neuromodulation.

Molecular characterization of the gonadal kisspeptin system: Cloning, tissue distribution, gene expression analysis and localization in sablefish (Anoplopoma fimbria).

The kisspeptin system plays pivotal roles in the regulation of vertebrate reproduction. Classically, kisspeptin produced in the brain stimulates brain gonadotropin-releasing hormone signaling, which in turn activates the pituitary-gonad axis. Expression of the kisspeptin system has also been documented in peripheral tissues, including gonads of mammals and fishes. However, the fish gonadal kisspeptin system remained uncharacterized. Herein we report identification and characterization of four kisspeptin system mRNAs (kisspeptin 1 (kiss1), kiss2, and G protein-coupled receptor 54-1 (gpr54-1) and gpr54-2) in sablefish, Anoplopoma fimbria. Sablefish predicted protein sequences were highly similar to those of other marine teleosts, but less so to freshwater teleosts. Tissue distribution analyses revealed that all four kisspeptin-system transcripts were expressed in both brain and gonad. However, kiss2 was the predominant transcript in the gonads and the only transcript detected in ovulated eggs. Ontogenetic analysis of kiss2 expression in juvenile sablefish gonads demonstrated that levels were low during sex differentiation but increased with fish size and gonadal development. Dramatic increases in kiss2 mRNA occurred during primary oocyte growth, while levels remained relatively low in testes. In situ hybridization revealed that kiss2 mRNA was localized to cytoplasm of perinucleolus stage oocytes, suggesting it could play a local role in oogenesis or could be synthesized and stored within oocytes as maternal mRNA. This represents the first study to focus on the gonadal kisspeptin system in fishes and provides important tools for further investigation of both the gonadal and brain kisspeptin systems in sablefish.

"True" Accessory Anterior Cerebral Artery: A Newly Reported Anterior Cerebral Arterial Anomaly and a Proposal for Its Classification.

If we use the same naming policy of middle cerebral arterial anomalies, then accessory anterior cerebral arteries (ACAs) should be applied for ACA anomalies originating from the ACA. We experienced such a rare ACA anomaly, which we referred to as true accessory ACA.

Neurite Damage in Patients with Migraine.

We examined neurite orientation dispersion and density imaging in patients with migraine. We found that patients with medication overuse headache exhibited lower orientation dispersion than those without. Moreover, orientation dispersion in the body of the corpus callosum was statistically negatively correlated with migraine attack frequencies. These findings indicate that neurite dispersion is damaged in patients with chronic migraine. Our study results indicate the orientation preference of neurite damage in migraine.

Efficacy of Lasmiditan as a Secondary Treatment for Migraine Attacks after Unsuccessful Treatment with a Triptan.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 h, patients took 50 mg of lasmiditan within 2 h of migraine onset. Patients recorded headache intensity and adverse events (AEs) caused by lasmiditan at 1, 2, and 4 h after the intake of an additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 h after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 h after lasmiditan intake. Our study revealed the significant headache relief provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short time. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Moyamoya Syndrome: Differential Diagnosis in Patients With Central Nervous System Symptoms and Hyperthyroidism.

Moyamoya syndrome, known as secondary moyamoya disease, is associated with various primary illnesses, such as brain tumor, meningitis, autoimmune disease, and thyrotoxicosis, and their relations are not clear. We report a rare case of moyamoya syndrome in a patient with Graves' disease. An 18-year-old woman was admitted to our hospital due to convulsions. She had symptoms of palpitations and fatiguability for half a year and transient numbness in her left upper extremity and dysarthria for a month. In physical findings, tachycardia and diffuse thyroid swelling were noted. A blood test revealed thyrotoxicosis and antithyroid antibody, and a diagnosis of Graves' disease was obtained. Brain magnetic resonance imaging (MRI) showed bilateral internal carotid artery occlusion. We finally diagnosed the patient with moyamoya syndrome caused by Graves' disease. Moyamoya disease or syndrome can cause symptoms like a stroke, sometimes requiring neurosurgical treatment. In our case, the therapy for Graves' disease resolved the symptoms. When diagnosing moyamoya disease, it is necessary to confirm whether there are any background diseases, such as Graves' disease.

An oocyte-specific astacin family protease, alveolin, is released from cortical granules to trigger egg envelope hardening during fertilization in medaka (Oryzias latipes).

It has long been hypothesized that in fishes the contents of cortical granules are involved in the hardening of egg envelope following fertilization. We previously purified the egg envelope hardening initiation factor from the exudates released from activated medaka (Oryzias latipes) eggs and tentatively termed this protein alveolin. Alveolin is a member of the astacin metalloprotease family and was proposed to be a protease which hydrolyzes ZPB at one restricted position to allow starting cross-linking with ZPC. Here, we investigated the complete pathway from biosynthesis and accumulation to secretion of alveolin. A single alveolin transcript was detected only in ovarian preparations, confirming the specific expression of alveolin in the ovary. In situ hybridization indicated that the alveolin mRNA is already expressed in the very early previtellogenic oocytes. However, immunocytochemical studies revealed that the appearance of alveolin protein was delayed until the beginning of the vitellogenic stage. The cortical granules isolated from unfertilized eggs contained a high molecular weight form of glycosylated alveolin with a 50kDa relative molecular mass. Hypotonic treatment burst isolated granules in vitro and transformed alveolin to a 21.5kDa form, which is the same size as that of natural alveolin released from eggs upon fertilization. This transformation was inhibited in the presence of leupeptin and 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF), suggesting that a serine protease is involved in alveolin activation upon fertilization. Furthermore, the phylogenetic relationship of alveolin with other vertebrate astacin family members was analyzed. The result shows that alveolin and its teleostean homologs make a new group which is separate from either the hatching enzyme, meprin and BMP1/tolloid groups.

Evaluation of cerebral function using iomazenil SPECT for patients with traumatic brain injury.

Traumatic brain injuries demonstrate various symptoms, including the disturbance of higher brain function, which is not visualized as a morphological lesion on magnetic resonance (MR) imaging. We examined the use of iomazenil single photon emission computed tomography (SPECT) for patients with traumatic brain injury and evaluated its diagnostic value. The study population included patients who were admitted to our hospital for traumatic brain injuries. All patients survived and were discharged from our hospital. MR imaging and iomazenil SPECT were examined during the acute and/or chronic phases. MR images were acquired using a 1.5-T clinical instrument. The T1- and T2-weighted and fluid-attenuated inversion recovery (FLAIR) axial images were evaluated. SPECT images were acquired using a multi-detector SPECT machine 3 h after the intravenous injection of 740 MBq of iomazenil. Axial, statistically analyzed images and stereotactic extraction estimation images were reconstructed and evaluated statistically based on the Z-score for each cerebral cortex. Iomazenil SPECT showed various lesions that were not demonstrated by MR imaging. Some clinical symptoms correlated with the iomazenil SPECT findings. Iomazenil SPECT is thus considered to be valuable for evaluating both brain lesions and the brain function after traumatic brain injury.

Extracranial Internal Carotid Arterial Dissection With Hypoglossal Nerve Palsy Caused by Cervical Self-Massage: A Case Report.

Internal carotid arterial dissection is a relatively rare condition that can cause neck pain and/or ischemic symptoms. Cranial nerve palsy caused by internal carotid arterial dissection is extremely rare. A 39-year-old male massaged his neck with his fingers. He experienced transient neck pain. After one week, he demonstrated hypoglossal nerve palsy. The radiological studies revealed extracranial internal carotid arterial dissection. Cervical self-massage may cause internal carotid arterial dissection and hypoglossal nerve palsy. For the patient with hypoglossal nerve palsy, the extracranial internal carotid artery should be investigated.

Idiopathic Normal Pressure Hydrocephalus With Multiple Sulcus Enlargements but No Ventricular Enlargement Resembling Brain Atrophy Over a Long Period Before Diagnosis: A Case Report.

The most common imaging findings in idiopathic normal pressure hydrocephalus (iNPH) are disproportionately enlarged subarachnoid space hydrocephalus, i.e., enlarged ventricles (Evans index >0.3), narrowing of the superior arcuate and median sulci, widening of the Sylvian fissure, and focal widening of the sulci of the brain. In the present study, we encountered an interesting case of a 73-year-old woman with iNPH with characteristic imaging findings of cerebral atrophy-like features and no prominent ventricular enlargement. Many cases might be difficult to diagnose as iNPH because of atypical imaging findings such as no prominent ventricular enlargement and so on. Even in cases with multiple atrophic sulcus openings without any prominent ventricular enlargement, the callosal angle and posterior commissure-level brain-ventricle ratio (BVR) could be helpful in the diagnosis, and bilateral opening of the occipitoparietal sulcus might be a key imaging finding.

Brain Abscess Due to Dental Sinusitis: A Case Report on Incomplete Infection Defense Associated With a Post-Fusion Linear Skull Fracture.

Brain abscess is a pyogenic disease secondary to a bacterial, tuberculous, or fungal infection of the brain; thus, early detection and treatment are of crucial importance. Herein, we present a case of a brain abscess arising from dental sinusitis due to an incomplete infection defense mechanism linked to a post-fusion linear skull fracture. The patient initially presented with a persistent headache, which was diagnosed as frontal sinusitis. Consequently, antibiotic treatment was started. However, due to a refractory response to antibiotics, MRI was performed, which revealed a brain abscess in the frontal lobe adjacent to the right frontal sinus measuring 40 mm in diameter. This abscess was surgically drained and cultured. Initially, the patient was treated with three antibiotics, which were eventually de-escalated. The cultures revealed nasal commensal bacteria, suggesting a direct spillover from sinusitis leading to a brain abscess. A tooth with root inflammation, which had been left untreated and resulted in bone melting of the maxillary sinus wall, was extracted. After more than eight weeks of antimicrobial therapy, improvement in the clinical and imaging findings was noted, and the patient was discharged. Brain abscesses may develop from sinusitis even after linear fractures have healed due to a continued incomplete infection defense mechanism. Moreover, root and sinus infections should undergo evaluation, including the upper dental crown using coronal computed tomography, and treatment should be initiated promptly.

Brain Microstructure and Brain Function Changes in Space Headache by Head-Down-Tilted Bed Rest.

INTRODUCTION: Several astronauts have experienced severe headaches during spaceflight, but no studies have examined the associated brain microstructure and functional changes. Head-down-tilted bed rest (HDBR) is a well-established method for studying the physical effects of microgravity on the ground. In this study, we analyzed the changes in brain microstructure and function during headache caused by HDBR using diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (R-fMRI).METHODS: We imaged 28 healthy subjects with DTI and R-fMRI in the horizontal supine position and HDBR. Using Tract-Based Spatial Statistics, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were compared between the headache and non-headache groups. Additionally, an analysis of functional connectivity (FC) was performed, followed by a correlation analysis between FC and numerical rating scale.RESULTS: HDBR caused headaches in 21 of 28 subjects. DTI analysis showed no significant change in fractional anisotropy after HDBR, whereas axial diffusivity, radial diffusivity, and mean diffusivity increased significantly. R-fMRI analysis showed a significant decrease in FC in several areas after HDBR. The headache group showed significantly higher FC before HDBR, and both groups showed higher FC after HDBR. Correlation analysis showed a positive correlation between FC and numerical rating scale before HDBR but negative after HDBR.DISCUSSION: We demonstrated the image change in the acute phase of space headache by HDBR using DTI and R-fMRI. Changes in brain microstructure and function specific to patients developing headaches may be evaluated by imaging.Goto M, Shibata Y, Ishiyama S, Matsumaru Y, Ishikawa E. Brain microstructure and brain function changes in space headache by head-down-tilted bed rest. Aerosp Med Hum Perform. 2023; 94(9):678-685.

Epidemiology of post-suboccipital craniotomy headache: A multicentre retrospective study.

The detailed epidemiology and mechanism of post-craniotomy headaches are not well understood. This study aimed to establish the actual clinical incidence and causes of post-craniotomy headaches. Suboccipital craniotomy surgeries performed in six institutions within the five-year study period were included. This study included 311 patients (138 males, 173 female; mean age, 59.3 years old). A total of 145 patients (49%) experienced post-craniotomy headaches. Microvascular decompression surgery, craniectomy and facial spasms were significant risk factors for post-craniotomy headaches. In most cases, the post-craniotomy headaches disappeared within one month; however, some patients suffered from long-term headaches. The craniotomy site and the methods of dura and skull closures should be individually determined for each patient. However, to prevent post-craniotomy headaches, craniotomy, instead of craniectomy, may be considered.

Conservative Treatment of Chronic Subdural Hematoma with Gorei-san.

Most asymptomatic patients with chronic subdural hematoma (CSDH) are followed conservatively but can require surgical treatment if the hematoma expands. We conducted a retrospective evaluation of the effect of Gorei-san on CSDH. This study included patients treated between April 2013 and March 2015. In total, 289 patients were diagnosed with CSDH and 110 patients received conservative management. Finally, 39 patients who met the requirements were registered. We retrospectively examined the age, gender, medical history, hematoma thickness, clarity of sulci below hematomas, and midline shift of the patients. The primary outcome was the median surgery-free interval, and the secondary results were the rate of CSDH shrinkage and surgery avoidance. A comparison of patient characteristics between the Gorei-san (G) and non-Gorei-san (NG) groups found no significant differences in the percentage of men, average ages, past history, thickness of CSDH (15.0 ± 3.1 mm vs. 15.3 ± 2.6 mm, p = 0.801), or midline shift (2.0 ± 2.7 mm vs. 4.0 ± 5.0 mm, p = 0.230). The median surgery-free interval was significantly different between the G and NG groups [n. r. vs. 41 days (95% CI: 5-79), log-rank p = 0.047]. The CSDH avoidance rate was not significantly different between the two groups (70.0% vs. 34.4%, p = 0.071). Additionally, the CSDH shrinkage rate was significantly different between the two groups (60.0% vs. 10.3%, p = 0.004). This retrospective study demonstrated that CSDH treatment with Gorei-san reduces hematoma significantly more than treatment that does not include Gorei-san.

Neoechinulin a imparts resistance to acute nitrosative stress in PC12 cells: a potential link of an elevated cellular reserve capacity for pyridine nucleotide redox turnover with cytoprotection.

Treatment of PC12 cells with fungus-derived alkaloid neoechinulin A for more than 12 h renders the cells resistant to subsequent superoxide (O2⁻)/nitric oxide (NO) insults derived from 3-morpholinosydnonimine (SIN-1). However, the underlying mechanism(s) remains largely unclear. To elucidate the mechanism(s), we assessed the specificity of the cytoprotection afforded by neoechinulin A treatment using other cytocidal stressors and also clarified the resulting cellular alterations, focusing on the antioxidant and metabolic enzymes systems. Neoechinulin A treatment for more than 12 h endowed PC12 cells with significant resistance to transient NO toxicity, but not persistent NO toxicity, bolus H2O2 toxicity, or oxidative insult from the redox cycling quinone menadione. Cellular antioxidant system profiling revealed no substantial potentiation of the activity of any antioxidant enzyme in lysate from the neoechinulin A-treated cells excluding glutathione (GSH) content, which was significantly decreased (>50%), resulting in a proportional compromise in the thiol-reducing activity of the intact cells. In addition, no differences were observed in the activity for any nicotinamide adenine dinucleotide (phosphate) reduced form (NAD(P)H)-generating enzyme, steady-state NAD(P)H/nicotinamide adenine dinucleotide (phosphate) oxidized form (NAD(P)⁺) ratios, or the levels of total NAD(P)H. Nevertheless, the neoechinulin A-treated intact cells exhibited increased NAD(P)H redox turnover when driven by extracellular tetrazolium. The structurally inactive analog preechinulin failed to protect cells against NO toxicity or induce these alterations, suggesting their link with the cytoprotective mechanism. These results suggest that neoechinulin A, despite disabling the GSH defense system, confers cytoprotection against nitrosative stresses by elevating the cellular reserve capacity for NAD(P)H generation, which could offset crippling of energy-supplying systems due to nitrosative stress.

A relaxin-like peptide purified from radial nerves induces oocyte maturation and ovulation in the starfish, Asterina pectinifera.

Gonad-stimulating substance (GSS) of starfish is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to the vertebrate luteinizing hormone (LH). Here, we purified GSS of starfish, Asterina pectinifera, from radial nerves and determined its amino acid sequence. The purified GSS was a heterodimer composed of 2 different peptides, A and B chains, with disulfide cross-linkages. Based on its cysteine motif, starfish GSS was classified as a member of the insulin/insulin-like growth factor (IGF)/relaxin superfamily. The cDNA of GSS encodes a preprohormone sequence with a C peptide between the A and B chains. Phylogenetic analyses revealed that starfish GSS was a relaxin-like peptide. Chemically synthesized GSS induced not only oocyte maturation and ovulation in isolated ovarian fragments, but also unique spawning behavior, followed by release of gametes shortly after the injection. Importantly, the action of the synthetic GSS on oocyte maturation and ovulation was mediated through the production of cAMP by isolated ovarian follicle cells, thereby producing the maturation-inducing hormone of this species, 1-methyladenine. In situ hybridization showed the transcription of GSS to occur in the periphery of radial nerves at the side of tube feet. Together, the structure, sequence, and mode of signal transduction strongly suggest that GSS is closely related to the vertebrate relaxin.