Role of sonic hedgehog signaling pathway in the regulation of ion channels: focus on its association with cardio-cerebrovascular diseases

Sonic hedgehog (SHH) signaling is vital for cell differentiation and proliferation during embryonic development, yet its role in cardiac, cerebral, and vascular pathophysiology is under debate. Recent studies have demonstrated that several compounds of SHH signaling regulate ion channels, which in turn affect the behavior of target cells. Some of these ion channels are involved in the cardio-cerebrovascular system. Here, we first reviewed the SHH signaling cascades, then its interaction with ion channels, and their impact on cardio-cerebrovascular diseases. Considering the complex cross talk of SHH signaling with other pathways that also affect ion channels and their potential impact on the cardio-cerebrovascular system, we highlight the necessity of thoroughly studying the effect of SHH signaling on ion homeostasis, which could serve as a novel mechanism for cardio-cerebrovascular diseases. (AU)

Role of sonic hedgehog signaling pathway in the regulation of ion channels: focus on its association with cardio-cerebrovascular diseases.

Sonic hedgehog (SHH) signaling is vital for cell differentiation and proliferation during embryonic development, yet its role in cardiac, cerebral, and vascular pathophysiology is under debate. Recent studies have demonstrated that several compounds of SHH signaling regulate ion channels, which in turn affect the behavior of target cells. Some of these ion channels are involved in the cardio-cerebrovascular system. Here, we first reviewed the SHH signaling cascades, then its interaction with ion channels, and their impact on cardio-cerebrovascular diseases. Considering the complex cross talk of SHH signaling with other pathways that also affect ion channels and their potential impact on the cardio-cerebrovascular system, we highlight the necessity of thoroughly studying the effect of SHH signaling on ion homeostasis, which could serve as a novel mechanism for cardio-cerebrovascular diseases. Activation of SHH signaling influence ion channels activity, which in turn influence ion homeostasis, membrane potential, and electrophysiology, could serve as a novel strategy for cardio-cerebrovascular diseases.

The effects of white matter hyperintensities on MEG power spectra in population with mild cognitive impairment.

Cerebrovascular disease is responsible for up to 20% of cases of dementia worldwide, but also it is a major comorbid contributor to the progression of other neurodegenerative diseases, like Alzheimer's disease. White matter hyperintensities (WMH) are the most prevalent imaging marker in cerebrovascular disease. The presence and progression of WMH in the brain have been associated with general cognitive impairment and the risk to develop all types of dementia. The aim of this piece of work is the assessment of brain functional differences in an MCI population based on the WMH volume. One-hundred and twenty-nine individuals with mild cognitive impairment (MCI) underwent a neuropsychological evaluation, MRI assessment (T1 and Flair), and MEG recordings (5 min of eyes closed resting state). Those participants were further classified into vascular MCI (vMCI; n = 61, mean age 75 ± 4 years, 35 females) or non-vascular MCI (nvMCI; n = 56, mean age 72 ± 5 years, 36 females) according to their WMH total volume, assessed with an automatic detection toolbox, LST (SPM12). We used a completely data-driven approach to evaluate the differences in the power spectra between the groups. Interestingly, three clusters emerged: One cluster with widespread larger theta power and two clusters located in both temporal regions with smaller beta power for vMCI compared to nvMCI. Those power signatures were also associated with cognitive performance and hippocampal volume. Early identification and classification of dementia pathogenesis is a crucially important goal for the search for more effective management approaches. These findings could help to understand and try to palliate the contribution of WMH to particular symptoms in mixed dementia progress.

Review on the Application of Hyperspectral Imaging Technology of the Exposed Cortex in Cerebral Surgery.

The study of brain science is vital to human health. The application of hyperspectral imaging in biomedical fields has grown dramatically in recent years due to their unique optical imaging method and multidimensional information acquisition. Hyperspectral imaging technology can acquire two-dimensional spatial information and one-dimensional spectral information of biological samples simultaneously, covering the ultraviolet, visible and infrared spectral ranges with high spectral resolution, which can provide diagnostic information about the physiological, morphological and biochemical components of tissues and organs. This technology also presents finer spectral features for brain imaging studies, and further provides more auxiliary information for cerebral disease research. This paper reviews the recent advance of hyperspectral imaging in cerebral diagnosis. Firstly, the experimental setup, image acquisition and pre-processing, and analysis methods of hyperspectral technology were introduced. Secondly, the latest research progress and applications of hyperspectral imaging in brain tissue metabolism, hemodynamics, and brain cancer diagnosis in recent years were summarized briefly. Finally, the limitations of the application of hyperspectral imaging in cerebral disease diagnosis field were analyzed, and the future development direction was proposed.

Primary multiple cerebral hydatid cysts in an immunocompetent, low-risk patient.

Cystic echinococcosis is a zoonotic infection that occurs worldwide. Humans are infected through ingestion of parasite eggs in contaminated food, water or through direct contact with infected dogs, which are the definite host. Humans serve accidentally as intermediate host, and occurrences are common in children and young adults. Cystic echinococcosis is endemic in Mediterranean, South American, Middle Eastern, Central Asia, East Africa countries and Australia. The liver is the most frequently involved organ, followed by lungs. Hydatid cysts have been reported only in 2% of cases in the brain. Primary cerebral hydatid disease is a rare entity, but should be considered in the differential diagnosis of cerebral lesions.

Anesthetic management of pediatric patients diagnosed with X-linked adrenoleukodystrophy: A single-center experience.

BACKGROUND: X-linked adrenoleukodystrophy is a progressive demyelinating disease that primarily affects males with an incidence of 1:20 000-30 000. The disease has a wide spectrum of phenotypic expression and may include adrenal insufficiency, cerebral X-linked adrenoleukodystrophy and adrenomyeloneuropathy. The condition has implications for the administration of anesthesia and reports of anesthetic management in those patients are limited at this point. AIM: To review the perioperative care, complications and outcomes of patients diagnosed with X-linked adrenoleukodystrophy at the University of Minnesota Masonic Children's Hospital. METHOD: After obtaining IRB approval, we performed a retrospective chart review of pediatric patients diagnosed with X-linked adrenoleukodystrophy who underwent either surgery or diagnostic/therapeutic procedures that included anesthesia services between January 2014 and December 2016. Data included demographics, American Society of Anesthesiologists classification, preoperative diagnosis, history of hematopoietic stem cell transplant, anesthetic approaches, airway management, medications used, intra- and postoperative complications, and patient disposition. RESULTS: We identified 38 patients who had a total of 166 anesthetic encounters. The majority of patients underwent procedures in the sedation unit (75.9%) and received a total intravenous anesthetic with spontaneous ventilation via a natural airway (86.1%). Preoperative adrenal insufficiency was documented in 87.3% of the encounters. Stress-dose steroids were administered in 70.5% of the performed anesthetics. A variety of anesthetic agents were successfully used including sevoflurane, isoflurane, propofol, midazolam, ketamine, and dexmedetomidine. There were few perioperative complications noted (6.6%) and the majority were of low severity. No anesthesia-related mortality was observed. CONCLUSIONS: With the availability of skilled pediatric anesthesia care, children with X-linked adrenoleukodystrophy can undergo procedures under anesthesia in sedation units and regular operating rooms with low overall anesthesia risk.

Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy.

AIMS: To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification. METHODS AND RESULTS: This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat (n = 537) and non-febuxostat groups (n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively (P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592-0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562-0.987; P = 0.041). CONCLUSION: Febuxostat lowers uric acid and delays the progression of renal dysfunction. REGISTRATION: ClinicalTrials.gov (NCT01984749).

Relationship between cognitive function and regulation of cerebral blood flow.

Ageing is the primary risk factor for cognitive deterioration. Given that the cerebral blood flow (CBF) or regulation of cerebral circulation is attenuated in the elderly, it could be expected that ageing-induced cognitive deterioration may be affected by a decrease in CBF as a result of brain ischemia and energy depletion. CBF regulation associated with cerebral metabolism thus likely plays an important role in the preservation of cognitive function. However, in some specific conditions (e.g. during exercise), change in CBF does not synchronize with that of cerebral metabolism. Our recent study demonstrated that cognitive function was more strongly affected by changes in cerebral metabolism than by changes in CBF during exercise. Therefore, it remains unclear how an alteration in CBF or its regulation affects cognitive function. In this review, I summarize current knowledge on previous investigations providing the possibility of an interaction between regulation of CBF or cerebral metabolism and cognitive function.

Rationale, design, and baseline characteristics of a study to evaluate the effect of febuxostat in preventing cerebral, cardiovascular, and renal events in patients with hyperuricemia.

BACKGROUND: Since uric acid is associated with cardiovascular and renal disease, a treatment to maintain blood uric acid level may be required in patients with hyperuricemia. This study aims to evaluate preventive effects of febuxostat, a selective xanthine oxidase inhibitor, on cerebral, cardiovascular, and renal events in patients with hyperuricemia compared to conventional treatment. METHODS AND RESULTS: This study is a prospective randomized open-label blinded endpoint study. Patient enrolment was started in November 2013 and was completed in October 2014. The patients will be followed for at least 3 years. The primary endpoint is a composite of cerebral, cardiovascular, and renal events, and all deaths including death due to cerebral, cardiovascular, and renal disease, new or recurring cerebrovascular disease, new or recurring non-fatal coronary artery disease, cardiac failure requiring hospitalization, arteriosclerotic disease requiring treatment, renal impairment, new atrial fibrillation, and all deaths other than cerebral or cardiovascular or renal disease. These events will be independently evaluated by the Event Assessment Committee under blinded information regarding the treatment group. The study was registered at ClinicalTrials.gov with the identifier NCT01984749.

Cerebral Disorders of the Adult Ruminant.

Although clinical impression suggests that cerebral disorders of adult ruminants are not very common, an understanding of the common differential diagnoses is important to maintaining animal and human health. The most common causes of cerebral dysfunction are metabolic, toxic, or infectious. Many of the diseases and disorders cannot be easily differentiated based on clinical signs or antemortem diagnostic tests alone. Knowing which diseases can be easily ruled in or out, and how, will help the practitioner make case management decisions and have broader impact through recognizing index cases of emergent diseases and reducing exposure to zoonotic pathogens.

Perspectives of In Vivo Bioluminescence Imaging: Application to Basic and Translational Neuroscience.

BACKGROUND: In vivo bioluminescence imaging has been used extensively for screening assays and for qualitative determination of localization of cells, in particular in cancer studies. OBJECTIVE: In this review we show the potential of this noninvasive molecular imaging modality to investigate gene activity, dynamic processes, and translational disease processes, all under true in vivo conditions with the specific focus on brain. RESULTS: We demonstrate a range of applications of bioluminescence imaging in basic and translational neuroscience. Here, emphasis is on the contribution of bioluminescence imaging of the brain to the elucidation of cellular and genetic mechanisms, understanding of dynamic processes, and to the discussion of disease characterization and therapeutic strategies.

Small vessel disease/white matter disease of the brain and its association with osteoporosis.

BACKGROUND: Evidence now suggests the role of neural effect on bone mass control. The effect of small vessel disease of the brain on osteoporosis has not been studied. The aim of this study was to investigate the association of white matter disease (WMD) of the brain with osteoporosis in the elderly. METHODS: In this retrospective cross-sectional study, 780 consecutive patient charts between 2010 and 2011 were reviewed in the Senior's Outpatient Clinic at the University of Alberta Hospital. Subjects with brain computerized tomography (CT) were included in the study. Subjects with incomplete information, intracranial hemorrhage, acute stroke, cerebral edema, and/or normal pressure hydrocephalus on the CT were excluded. WMD was quantified on CT using Wahlund's scoring protocol. Osteoporosis information was obtained from the chart, which has been diagnosed based on bone mineral density (BMD) information. Logistic regression analysis was done to determine the association of WMD severity with osteoporosis after controlling for confounding vascular risk factors. RESULTS: Of the 505 subjects who were included in the study, 188 (37%) had osteoporosis and 171 (91%) of these osteoporotic subjects were females. The mean age was 79.8 ± 7.04 years. The prevalence of WMD in osteoporosis subjects was 73%. In the unadjusted logistic regression analysis, there was a significant association between WMD severity and osteoporosis (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.05 - 1.14; P < 0.001) and the significance remained in the adjusted model, after correcting for age, sex and all vascular risk factors (OR: 1.11; 95% CI: 1.05 - 1.18; P < 0.001). CONCLUSION: WMD severity of the brain was associated with osteoporosis in the elderly.

Clinical application of characteristic manifestation of MR diffusion weighted imaging at 3.0T in cerebral diseases / 实用放射学杂志

Objective To explore the value of characteristic manifestation of diffusion-weighted images at 3.0T MR system in cer-ebral disease.Methods 120 patients with cerebral disease diagnosed by MR diffusion-weighted images (fat suppression effect,T2 blackout effect,T2 shine-through effect,T2 washout effect)underwent routine MR scan,including echo planar imaging-diffusion weighted imaging (EPI-DWI)and apparent diffusion coefficient (ADC)map,whose characteristic manifestations of DWI were retro-spectively analyzed.Results 1 5 cases of lipoma and 8 cases without fat lesions were diagnosed with fat suppression effect.13 cases of acute cerebral hematoma,1 1 cases of hemorrhagic cerebral infarction and 1 6 cases of micro bleeding of missed diagnosis or small cavernous hemangioma were diagnosed with T2 blackout effect.1 5 cases of epidermoid cyst,5 cases of choroid plexus cyst were di-agnosed with T2 shine-through effect.1 5 cases of posterior reversible encephalopathy syndrome and 22 cases of brain tumor were di-agnosed with T2 washout effect.Conclusion Comprehensive use of the characteristic manifestation of EPI-DWI and ADC map can help the diagnosis of cerebral disease.

A glance at Live Interventional Neuroradiology & Neurosurgery Course 2009 / 介入放射学杂志

The annual Live Interventional Neuroradiology & Neurosurgery Course (LINNC) is one of the most important congresses in the neurosurgery and neuroradiology field. LINNC 2009 was held on May 25th this year and lasted for 3 days. In this article, the authors introduced the main points of the congress The congress mainly discussed some hot topics at present time, including both the clinical and fundamental studies of cerebral arteriovenous malformation. Ischemic cerebral disease and intracranial aneurysm, etc. Both neurological and neuroradiological case demonstrations related to the topics, and the main course of the congress were altemately performed. Recent advances in imaging technique and clinical application, such as Dyna-CT and Xper-CT, were also presented on the congress.

A glance at Live Interventional Neuroradiology & Neurosurgery Course 2009 / 介入放射学杂志

The annual Live Interventional Neuroradiology & Neurosurgery Course(LINNC) is one of the most important congresses in the neurosurgery and neuroradiology field.LINNC 2009 was held on May 25th this year and lasted for 3 days.In this article, the authors introduced the main points of the congress.The congress mainly discussed some hot topics at present time, including both the clinical and fundamental studies of cerebral arteriovenous malformation, ischemic cerebral disease and intracranial aneurysm, etc.Both neurological and neuroradiological case demonstrations related to the topics, and the main course of the congress were alternately performed.Recent advances in imaging technique and clinical application, such as Dyna-CT and Xper-CT, were also presented on the congress.