[Mechanism of action and clinical trial results of Lecanemab (Leqembi® 200†|mg, 500†|mg for Intravenous Infusion), a novel treatment for Alzheimer's disease].

Lecanemab is a humanized monoclonal antibody directed against human soluble amyloid-ß aggregates. It was developed for the treatment of early Alzheimer's disease (mild cognitive impairment or mild dementia stage of Alzheimer's disease). Among the amyloid-ß (Aß) involved in Alzheimer's disease, Lecanemab selectively binds to the highly neurotoxic Aß protofibrils, and is thought to reduce Aß protofibrils and amyloid plaques (Aß plaques) in the brain. The efficacy and safety of Lecanemab in early Alzheimer's disease were investigated in an international Phase II placebo-controlled study (Study 201) and an international Phase III placebo-controlled study (Study 301). Both studies included Japanese subjects. Lecanemab was given accelerated approval in the United States in January 2023, followed by traditional approval in July 2023. In Japan, it was approved for "control of the progression of mild cognitive impairment or mild dementia stage of Alzheimer's disease" in September 2023, and was added to the NHI drug price list in December 2023.

[The Roles of Aß in Alzheimer's Disease: In Light of the Latest Findings].

The 'amyloid hypothesis', initially put forward in 1992, posits that amyloid ß protein (Aß) contributes to neurodegeneration through aberrant aggregation. In the process of this aberrant aggregation, Aß forms oligomers, protofibrils, and mature fibrils, ultimately developing plaques. These mature fibrils and plaques were believed to be the culprits behind the neurotoxicity and neurodegeneration seen in Alzheimer's disease (AD). However, growing evidence in recent years has led to the 'Aß oligomer hypothesis', which suggests that the intermediate forms of aggregates, such as oligomers and protofibrils, exhibit stronger neurotoxicity than the mature forms. Consequently, efforts have been made to develop anti-Aß antibody drugs that specifically target these intermediate aggregates. Such interventions hold promise as disease-modifying treatments for AD.

Phenothiazine cyclic hexamers: synthesis, properties, and complexation behavior with C60.

Phenothiazine cyclic hexamers linked at the 3,7-positions were synthesized. Effects of the cyclic structure as well as substituent effects of the nitrogen atom were disclosed. Furthermore, the cyclic hexamer encapsulated C60 inside the ring in a 1 : 1 ratio giving a Saturn-type complex in solution. The structure and interactions were discussed based on DFT calculations.

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study.

OBJECTIVE: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). METHODS: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. RESULTS: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. CONCLUSION: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

[Diffuse infiltrating primary cerebellar glioma involving the brainstem: a case report].

An 85-year-old woman was admitted to our hospital with unsteady gait, dizziness, nausea, and vomiting. MRI revealed characteristic abnormal signals in the bilateral cerebellar hemispheres. A brain biopsy was performed which confirmed a definitive histological diagnosis of diffuse glioma. Follow-up MRI showed diffuse abnormal signals that extended from the cerebellum to the brainstem through the cerebellar peduncle without mass formation. Her general condition gradually deteriorated even with the best supportive care, and she died 195 days after admission. Gliomatosis cerebri is characterized by a diffuse infiltrating growth pattern without mass formation in the brain. This case showed a similar proliferation mode from the cerebellum to the brain stem without mass formation. This case was diagnosed based on MRI and pathological findings. Only five similar cases have been previously reported, and compared to these reports, the patient in the present case was the oldest with the poorest prognosis. The histopathological features may influence the appropriate treatment and the prognosis. This disorder is a very rare condition; thus, when we encountered this patient showing cerebellar ataxia with diffuse abnormal MRI signals without mass formation in the cerebellum and brainstem, a brain biopsy was necessary to establish the definitive diagnosis.

Study on the Preparation Method of Quality-Assured In-Hospital Drug Formulation for Children-A Multi-Institutional Collaborative Study.

The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification.

A series of boron difluoride complexes of azinylcarbazoles: synthesis and structure-property relationships.

A series of boron difluoride (BF2) complexes of azinylcarbazoles 1b-1h were synthesized, and the effects of the structure of azine moieties on the photophysical and electrochemical properties of the BF2 complexes were clarified. UV-vis analysis of 1b with quinoline, 1c with isoquinoline, and fully fused 1d revealed that fusion with a benzene ring to a pyridylcarbazole BF2 complex (1a) resulted in red shifts of longest-maximum absorption wavelengths (λmax). UV-vis analysis of 1e and 1f with pyrimidine, 1g with pyridazine, and 1h with pyrazine revealed that substitution of a carbon atom to a nitrogen atom in 1a also resulted in red shifts of λmax. The fluorescence quantum yields (Φf) decreased from 1a to 1b-1h, and especially, the fluorescence of 1e, 1g, and 1h was quenched in solution. At 77 K, the emission intensities of 1b-1h were significantly increased compared with those at ambient temperature, and they also exhibited phosphorescence with relatively narrow energy gaps between the singlet and triplet excited states. These results on the emission at 77 K indicate that the quench of fluorescence from 1e, 1g, and 1h at ambient temperature originates from both internal conversions and intersystem crossing. In the solid state, all of the complexes including 1e, 1g, and 1h exhibited emission. Distinctive aggregation-induced emission properties were observed for 1e-1h. Electrochemical measurements revealed that the replacement of the pyridine moiety in 1a with azine moieties reduced electrochemical gaps mainly due to a decrease in the LUMO levels. The effects of azine moieties on electronic structures were also discussed based on theoretical calculations.

Phenothiazine-, Dihydroacridine-, and Acridone-Based Boron Difluoride Complexes: Synthesis and Structure-Property Relationships.

Boron difluoride complexes of phenothiazine, 9,10-dihydroacridine, and acridone derivatives with a pyridyl group were synthesized. Their structures, dynamic conformational behaviors, and photophysical properties, including solid-state fluorescence, were disclosed. The effects of the oxidation state of the sulfur atom in the phenothiazine derivatives on their properties were also clarified.

Serum periostin levels in adolescents.

BACKGROUND: The significance of periostin as a biomarker of Th2-induced airway inflammation has recently been highlighted in adult patients with allergic diseases. It may help identify drug-responsive inflammatory phenotypes, particularly in children. However, little is known about the usefulness of this parameter as a biomarker for allergic diseases in children. Furthermore, it is not known how much adolescent bone metabolism affects allergic inflammation. OBJECTIVE: To evaluate the relationship between serum periostin levels and allergic diseases in adolescents, we investigated periostin levels and the prevalence of allergic diseases. METHODS: We conducted a cross-sectional observational study of 100 males and females in two age groups: age 9-12 years (pre-early adolescence) and 13-15 years (post-early adolescence). Serum periostin levels were determined using Enzyme-Linked Immuno Sorbent Assay (ELISA). Presence of allergic diseases and allergy sensitization were obtained via a self-reported survey and the Multiple Antigen Simultaneous Test (MAST). The protocol was registered in a clinical trial registry as UMIN 000036051. RESULTS: There were no significant differences in serum periostin levels between pre-early and post-early adolescents. There were no differences by gender. Age and Body Mass Index were not significantly associated with serum periostin levels. Periostin levels were elevated in adolescents with allergic diseases overall compared to healthy adolescents [mean (95%CI): 41.6 (33.4, 49.7) vs. 28.6 (21.9, 35.3) ng/ml; P < 0.05]. CONCLUSIONS: The effects of bone metabolism on serum periostin levels may be limited at 9-15 years of age. Further studies are required to determine reference values in adolescents.

Effectiveness of a Gelatin-Thrombin Matrix Sealant (Floseal®) for Reducing Blood Loss During Microendoscopic Decompression Surgery for Lumbar Spinal Canal Stenosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To investigate the effectiveness and safety of a gelatin-thrombin matrix sealant (GTMS) during microendoscopic laminectomy (MEL) for lumbar spinal canal stenosis (LSCS). METHODS: This study included 158 LSCS cases on hemostasis-affecting medication who underwent MEL by a single surgeon between September 2016 and August 2020. Patients were divided into 2 groups depending on whether GTMS was used (37 cases, Group A) or not (121 cases, Group B). Perioperative data related to bleeding or postoperative spinal epidural hematoma (PSEH) was investigated. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) score for low back pain. RESULTS: The mean intraoperative blood loss per level was greater in Group A (26.0 ± 20.3 g) than in Group B (13.6 ± 9.0 g), whereas the postoperative drainage volume was smaller in Group A (79.1 ± 42.5 g) than in Group B (97.3 ± 55.6 g). No revision surgeries for PSEH were required in Group A, while 2 (1.7%) revisions were required in Group B (P = .957). The median JOA score improved significantly from the preoperative period to 1-year postoperatively in both Group A and B (total score, 16.0-23.5 and 17.0-25.0 points, respectively). CONCLUSIONS: The use of GTMS during MEL for LSCS may be associated with a reduction in postoperative drainage volume. The revision rate for PSEH was not affected significantly by the use of GTMS. Clinical outcomes (represented by the JOA score) were significantly improved after the surgery, regardless of GTMS use during MEL.

Balance dysfunction the most significant cause of in-hospital falls in patients taking hypnotic drugs: A retrospective study.

PURPOSE: Preventing falls in patients is one of the most important concerns in acute hospitals. Balance disorder and hypnotic drugs lead to falls. The Standing Test for Imbalance and Disequilibrium (SIDE) is developed for the evaluation of static standing balance ability. There have been no reports of a comprehensive assessment of falls risk including hypnotic drugs and SIDE. The purpose of this study was to investigate the fall rate of each patient who took the hypnotic drug and the factor associated with falls. METHODS: Fall rates for each hypnotic drug were calculated as follows (number of patients who fell/number of patients prescribed hypnotic drug x 100). We investigated the hypnotic drugs as follows; benzodiazepine drugs, Z-drugs, melatonin receptor agonists, and orexin receptor antagonists. Hypnotic drug fall rate was analyzed using Pearson's chi-square test. Decision tree analysis is the method we used to discover the most influential factors associated with falls. RESULTS: This study included 2840 patients taking hypnotic drugs. Accidents involving falls were reported for 211 of inpatients taking hypnotic drugs. Z-drug recipients had the lowest fall rate among the hypnotic drugs. We analyzed to identify independent factors for falls, a decision tree algorithm was created using two divergence variables. The SIDE levels indicating balance disorder were the initial divergence variable. The rate of falls in patients at SIDE level ≦ 2a was 14.7%. On the other hand, the rate of falls in patients at SIDE level ≧ 2b was 2.9%. Gender was the variable for the second classification. In this analysis, drugs weren't identified as divergence variables for falls. CONCLUSION: The SIDE balance assessment was the initial divergence variable by decision tree analysis. In order to prevent falls, it seems important not only to select appropriate hypnotic drugs but also to assess patients for balance and implement preventive measures.

Neurotropin protects rotator cuff tendon cells from lidocaine-induced cell death.

BACKGROUND: Local anesthetics often are used in rotator cuff tears as therapeutic tools, although some cases have reported that they have detrimental effects. Neurotropin (NTP) is used widely in Japan as a treatment for various chronic pain conditions and is shown to have protective effects on cartilage and nerve cells. In this study, we investigated the protective effect of NTP against lidocaine-induced cytotoxicity. METHODS: Tenocytes from rotator cuff tendons were incubated with lidocaine, NTP, lidocaine with NTP, and a control medium. Cell viability was evaluated using the WST-8 assay. Cell apoptosis was detected via annexin V staining using flow cytometry. The expression of BCL-2 and cytochrome c, which are involved in the intrinsic mitochondrial pathway of apoptosis, was evaluated via Western blotting and immunohistochemical staining. RESULTS: In the cell viability assay, lidocaine decreased cell viability in a dose-dependent manner, and NTP did not affect cell viability. Moreover, NTP significantly inhibited the cytotoxic effect of lidocaine. The flow cytometry analysis showed that lidocaine significantly induced apoptosis in tenocytes, and NTP considerably inhibited this lidocaine-induced apoptosis. Western blotting experiments showed that lidocaine decreased the protein expression of BCL-2, and that NTP conserved the expression of BCL-2, even when used with lidocaine. Immunohistochemical staining for cytochrome c showed that 0.1% lidocaine increased cytochrome c-positive cells, and NTP suppressed lidocaine-induced cytochrome c expression. CONCLUSIONS: NTP suppresses lidocaine-induced apoptosis of tenocytes by inhibiting the mitochondrial apoptotic pathway. Intra-articular/ bursal injection of NTP with lidocaine could protect tenocytes in rotator cuff tendons against lidocaine-induced apoptosis.

Invasive Fungal Rhinosinusitis with Orbital Apex Syndrome Leading to Brain Abscess in a Patient with Ulcerative Colitis.

We report the case of a 65-year-old male who presented with a 1-week history of right periorbital pain and progressive visual loss. He had a history of ulcerative colitis and was taking oral corticosteroids and mesalazine. Neurological and radiological examination demonstrated a rare case of invasive fungal rhinosinusitis that began with orbital apex syndrome. Initial endoscopic sinus surgery was performed and fungal culture identified Aspergillus fumigatus. Although antifungal treatment was started empirically before the operation, the patient had improved orbital pain but continued to have decreased right vision. Five months after the first surgical procedure, his condition deteriorated, including loss of consciousness, and a right temporal lobe abscess was found and surgically drained. Since then, the patient received antifungal treatment for 4 years without recurrence. Invasive fungal rhinosinusitis with orbital apex syndrome should be treated with long-term postoperative antifungal medication. It should be noted that even in immunosuppressive individuals such as ulcerative colitis, fungal rhinosinusitis with orbital apex syndrome may become severe.

Characteristic appearance of the oropharynx in patients with postnasal drip (PND)-induced cough.

INTRODUCTION: Post-nasal drip (PND)-induced cough is a common cause of chronic cough. However, there is little known about the characteristic physical findings of this condition. OBJECTIVES: We investigated views of the pharyngeal wall in patients with PND-induced cough using a handy endoscopic images. METHODS: The subjects were 135 consecutive patients referred to our hospital with a sensation of something "dripping down the throat" as one of their symptoms. Physical findings for the oropharynx were examined using Wi-Fi endoscope camera. The difference in probability of symptoms in patients with acute cough and those with subacute/chronic cough was assessed using a Bayesian Fisher exact test on a 2 × 2 table. RESULTS: Among the patients, 105 (78%) complained of cough, 78 (58%) of acute cough, 20 (15%) of subacute cough, and 7 (5%) of chronic cough; and 71 (53%) had coexisting asthma. Using Bayesian inference, a sore or scratchy throat and fever were more common in patients with acute cough than in those with subacute/chronic cough. In endoscopic images of the oropharynx, a reddish curtain sign on the posterior pharyngeal wall behind the palatopharyngeal arch was found in 121 patients (90%). CONCLUSION: Patients with acute PND-induced cough have a component of acute upper respiratory infection, because of high probability of a sore or scratchy throat and fever as symptom. A reddish curtain sign may be a useful finding for identifying PND-induced cough in these cases.

Effect of fexofenadine/pseudoephedrine combination tablet on nasal obstruction in patients with allergic rhinitis using rhinomanometry: A randomized controlled trial.

BACKGROUND: A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited. OBJECTIVE: We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods. METHODS: In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845. RESULTS: The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period. CONCLUSIONS: We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

A comparison in the ability to detect diabetic retinopathy between fasting plasma glucose and HbA1c levels in a longitudinal study.

Aims: The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. In this study, we verified which of HbA1c and fasting plasma glucose (FPG) is more effective for detecting the diabetic retinopathy longitudinally in a Japanese population. Materials and Methods: The study subjects underwent health examinations twice (including eye test and questionnaire of lifestyle and health) in 2008-2009 (baseline) and in 2012-2013 (4-year follow-up). Both non-DM and DM patients at baseline were included as the participants. Of these participants, who had not been diagnosed with retinopathy at the baseline survey (n = 2427; 2150 men and 277 women) had eye fundus photographs taken four years later (follow-up survey). The odds ratios of incidence of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for sex and age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results: The odds ratios (95% confidence intervals) of incidence of retinopathy by HbA1c level categories, in ascending order, were 1.0 (ref.), 5.66 (1.14-28.26), 1.69 (0.24-12.04), 3.03 (0.50-18.28), 1.04 (0.09-11.59), 4.73 (0.78-28.69), 4.12 (0.74-22.85) and 24.47 (5.61-106.75). For both FPG and HbA1c levels, the odds ratio for the development of retinopathy increased linearly with the increases in the levels FPG and HbA1c, and no clear threshold was observed. The AUC values (SE) for FPG and HbA1c were almost the same, at 0.750 (0.046) and 0.732 (0.048). Conclusions: It was clarified that the higher the level of FPG and HbA1c was, the higher the incidence of retinopathy after 4 years was. There was no clear threshold. The detection ability of the incidence of retinopathy was almost the same between FPG and HbA1c, suggesting it is possible to detect the risk of retinopathy by HbA1c only.

Cetuximab and paclitaxel combination therapy for recurrent basaloid squamous cell carcinoma in the ethmoid sinus.

Basaloid squamous cell carcinoma (BSCC), a histologically distinctive variant of squamous cell carcinoma comprising basal cell carcinoma and squamous cell carcinoma, is aggressive and shows a poor prognosis because of frequent lymph node invasion and distant metastases. To date few articles regarding chemotherapy for metastatic disease have been reported, thus feasible chemotherapy is not well established. Cetuximab is a monoclonal antibody for epithelial growth factor receptor (EGFR), which has great efficacy for head and neck squamous cell carcinoma due to EGFR signaling pathway blockage. Because BSCC also highly expresses EGFR, cetuximab may be effective for BSCC. We report here a first case of recurrent BSCC in the ethmoid sinus with intracranial extension treated with cetuximab-based chemotherapy, which revealed great response in a 40-year-old man. Positron emission tomography (PET) revealed no lymph node or distant metastasis. The patient underwent chemoradiotherapy 66 Gy in 33 fractions with triweekly 100 mg/m2 cisplatin. However, 12 weeks after treatment completion PET revealed a residual tumor at the primary cancer site. Combination therapy with weekly paclitaxel and cetuximab was started, and complete response was observed 2 months from treatment initiation. The patient has maintained complete response for 32 months, and no tumor regrowth has been observed.

Arylene-hexaynylene and -octaynylene macrocycles: extending the polyyne chains drives self-association by enhanced dispersion force.

Tetraalkoxyphenanthrylene-hexaynylene and -octaynylene macrocycles, which represent the first examples of isolable arylene-alkynylene macrocycles (AAMs) that contain polyyne chains longer than tetrayne, were synthesized and their self-association behavior was examined. Extending the polyyne chain from diyne to tetrayne, hexayne, and octayne exponentially increased the self-association constant of the macrocycles.

Monoradicals and Diradicals of Dibenzofluoreno[3,2-b]fluorene Isomers: Mechanisms of Electronic Delocalization.

The preparation of a series of dibenzo- and tetrabenzo-fused fluoreno[3,2-b]fluorenes is disclosed, and the diradicaloid properties of these molecules are compared with those of a similar, previously reported series of anthracene-based diradicaloids. Insights on the diradical mode of delocalization tuning by constitutional isomerism of the external naphthalenes has been explored by means of the physical approach (dissection of the electronic properties in terms of electronic repulsion and transfer integral) of diradicals. This study has also been extended to the redox species of the two series of compounds and found that the radical cations have the same stabilization mode by delocalization that the neutral diradicals while the radical anions, contrarily, are stabilized by aromatization of the central core. The synthesis of the fluorenofluorene series and their characterization by electronic absorption and vibrational Raman spectroscopies, X-ray diffraction, SQUID measurements, electrochemistry, in situ UV-vis-NIR absorption spectroelectrochemistry, and theoretical calculations are presented. This work attempts to unify the properties of different series of diradicaloids in a common argument as well as the properties of the carbocations and carbanions derived from them.

Regulatory effects of cervical sympathetic trunk and renal sympathetic nerve activities on cerebral blood flow during head-down postural rotations.

This study attempts to clarify the neural control of cerebral blood flow (CBF) during head-down postural rotation, which induces a cephalad fluid shift in urethane-anesthetized rats. The animals were placed on a table, tilted to a 45° head-down position over 5 s and maintained in that position. Head-down rotation (HDR) induced a transient decrease (8 ± 3 mm Hg; mean ± SE) in mean arterial blood pressure (ABP) at 7.3 ± 0.3 s after the onset of HDR. The pressure returned to the pre-HDR level within 1 min in the head-down position. Pretreatment with hexamethonium bromide suppressed the HDR-elicited decrease in ABP, suggesting that the decrease in ABP was induced by the suppression of autonomic neural outflow. The administration of phenoxybenzamine (PB), an α-adrenergic antagonist, also eliminated the HDR-elicited decrease in ABP, suggesting that this decrease was elicited by the suppression of α-adrenergic vascular tone. To test sympathetic outflow during HDR, renal sympathetic nerve activity (RSNA) and cervical sympathetic trunk (CST) activity (CSTA) were recorded. RSNA was transiently suppressed at 2.3 ± 0.4 s after HDR onset, followed by a decrease in ABP, suggesting that this decrease was, at least in part, induced by the suppression of sympathetic nerves. CSTA did not change significantly during HDR. These results suggest that HDR suppresses sympathetic nerves in the lower body rather than in the head, which might result in a decrease in ABP. To test the effect of the decrease in ABP due to sympathetic activity on CBF during HDR, changes in CBF during HDR were measured. CBF did not change significantly during HDR in the control group after the administration of an α-receptor blocker or after denervation of the CSTs. These results suggest that the impact of the CSTs on CBF is likely to be limited by a rapid increase in CBF due to HDR-elicited cephalad fluid shift and that CBF autoregulation proceeds through an alternative mechanism involving the myogenic properties of cerebral vessels.