Ultra-deep through-skull mouse brain imaging via the combination of skull optical clearing and three-photon microscopy

Optical microscopy has enabled in vivo monitoring of brain structures and functions with high spatial resolution. However, the strong optical scattering in turbid brain tissue and skull impedes the observation of microvasculature and neuronal structures at large depth. Herein, we proposed a strategy to overcome the influence induced by the high scattering effect of both skull and brain tissue via the combination of skull optical clearing (SOC) technique and thee-photon fluorescence microscopy (3PM). The Visible-NIR-II compatible Skull Optical Clearing Agents (VNSOCA) we applied reduced the skull scattering and water absorption in long wavelength by refractive index matching and H2O replacement to D2O respectively. 3PM with the excitation in the 1300-nm window reached 1.5 mm cerebrovascular imaging depth in cranial window. Combining the two advanced technologies together, we achieved so far the largest cerebrovascular imaging depth of 1 mm and neuronal imaging depth of >700 μm through intact mouse skull. Dual-channel through-skull imaging of both brain vessels and neurons was also successfully realized, giving an opportunity of non-invasively monitoring the deep brain structures and functions at single-cell level simultaneously.

Secondary neurogenic prosopalgia in a neurological clinic

Annotation. Prosoplgia is one of the most common pain syndromes in the craniofacial area. In the clinic practice of the facial pain treatment, neurogenic prosopalgia accounts for 25-30% of cases. The aim of the study was to evaluate the clinical, laboratory and functional parameters of patients with secondary neurogenic prosopalgia at neurological department. The medical histories of 21 patients (17 (81.0%) women and 4 (19.0%) men) suffered from secondary neurogenic prosopalgia were analyzed retrospectively. The clinical picture, data of general blood and urine tests, biochemical blood tests, neuroimaging, electrophysiological and ultrasonic research methods were evaluated. A preliminary comparison of retrospective patients quality indicators was assessed using simple mathematical methods. A predominant lesion of the I branch of the trigeminal nerve was shown in elderly women with postherpetic neuralgia, while other reasons of secondary neuralgia of the II and III branches of the trigeminal nerve more often caused left-sided lesions. Primary diseases included: herpetic ganglionitis, malignant tumor of the bladder with herpetic complications, sinusitis, dental diseases, meningoencephalitis, atherosclerosis of the brain vessels, concussion of the brain. The features of the clinical picture of each case were evaluated, as well as the characteristic concomitant groups of symptoms, among which were determined cephalgic, asthenoneurotic, vestibulo-atactic, vegetative dystonia, pyramidal syndromes. Among the general and functional studies carries out, attention was drawn to the increase of ESR in almost half of the patients, even without exacerbation of the primary disease, as well as the presence of metabolic disorders in the myocardium according to the electrocardiogram in 47.6% of cases, including in relatively young individuals. Thus, the problem of secondary neurogenic prosopalgia, despite the modern treatment, remains relevant.

Ultrasound in the Diagnosis of Perinatal Ischemic Strokes (Literature Review with Their Own Clinical Observations)

The issues of early diagnosis of perinatal arterial stroke (PAII) continue to be discussed in the domestic and foreign literature. Along with MRI, the ultrasound method allows to identify foci of ischemia of different localization and sizes in newborns. During ultrasound, we identified 29 cases of PAIA of different localization in children of different gestational and postnatal age. Analysis of our own and published data showed that up to 32 weeks of gestational development, AII develops in the lenticular-striar basin, and later in the cortical-subcortical region. Diagnostic capabilities of ultrasound in PAII can be significantly expanded by using ultrasound duplex scanning of brain vessels. Our observations showed that the nature of changes in Doppler parameters depends on the localization of the affected vascular basin and on the duration of cerebrovascular disorders

Novel Technique to Measure Pulse Wave Velocity in Brain Vessels Using a Fast Simultaneous Multi-Slice Excitation Magnetic Resonance Sequence

In this study, we proposed a novel pulse wave velocity (PWV) technique to determine cerebrovascular stiffness using a 3-tesla magnetic resonance imaging (MRI) to overcome the various shortcomings of existing PWV techniques for cerebral-artery PWV, such as long scan times and complicated procedures. The technique was developed by combining a simultaneous multi-slice (SMS) excitation pulse sequence with keyhole acquisition and reconstruction (SMS-K). The SMS-K technique for cerebral-artery PWV was evaluated using phantom and human experiments. In the results, common and internal carotid arteries (CCA and ICA) were acquired simultaneously in an image with a high temporal resolution-of 48 ms for one measurement. Vascular signals at 500 time points acquired within 30 s could generate pulse waveforms of CCA and ICA with 26 heartbeats, allowing for the detection of PWV changes over time. The results demonstrated that the SMS-K technique could provide more PWV information with a simple procedure within a short period of time. The procedural convenience and advantages of PWV measurements will make it more appropriate for clinical applications.

Notch3 Mutation Detection in Stroke Patients and Selective Nanoliposome in Stroke Alleviation in a Mouse Model

This study analyzed the correlation between the Notch3 mutation and stroke by testing an effective nanoparticle-loaded aspirin in stroke therapy. Fifty patients with ischemic stroke were followed for two years, and fifty healthy persons served as the control group. By RT-PCR, this study revealed that the Notch3 mutation existed in ischemic stroke patients who were more likely to have a family history, small vessel lesions, relatively frequent cerebral hemorrhage, and poor long-term prognosis. Liposome-aspirin-chitosan nanoparticle (LACN) was constructed as a nano-composite for stroke treatment. Notch3 Arg170Cys knock-in mice were prepared as a mutant Notch3 mouse model to test the LACN infiltration efficiency and observe the anti-stroke capacity. We found that LACN could better transport aspirin into brain vessels than the Polyethyleneimine (PEI) delivery system. However, in the Notch3 mutation mouse model, cerebral infarction and hemorrhage often occurred after being treated with aspirin. Still, LACN better prolongs the half-life of aspirin, rescues the pathological alteration of stroke in the brain, and reduces inflammatory reaction and oxidative stress response. In conclusion, the Notch3 mutation is closely related to stroke occurrence, and LACN may be a better choice for stroke therapy in the future.

Definition and extraction of 2D shape indices of intracranial aneurysm necks for rupture risk assessment

Purpose Intracranial aneurysms are local dilations of brain vessels. Their rupture, as well as their treatment, is associated with high risk of morbidity and mortality. In this work, we propose shape indices for aneurysm ostia for the rupture risk assessment of intracranial aneurysms. Methods We analyzed 84 middle cerebral artery bifurcation aneurysms (27 ruptured and 57 unruptured) and their ostia, with respect to their size and shape. We extracted 3D models of the aneurysms and vascular trees. A semi-automatic approach was used to separate the aneurysm from its parent vessel and to reconstruct the ostium. We used known indices to quantitatively describe the aneurysms. For the ostium, we present new shape indices: the 2D Undulation Index (UI$$_\mathrm{2D}$$ 2 D ), the 2D Ellipticity Index (EI$$_\mathrm{2D}$$ 2 D ) and the 2D Noncircularity Index (NCI$$_\mathrm{2D}$$ 2 D ). Results were analyzed using the Student t test, the Mann–Whitney U test and a correlation analysis between indices of the aneurysms and their ostia. Results Of the indices, none was significantly associated with rupture status. Most aneurysms have an NCI$$_\mathrm{2D}$$ 2 D below 0.2. Of the aneurysms that have an NCI$$_\mathrm{2D}$$ 2 D above 0.5, only one is ruptured, which indicates that ruptured aneurysms often have a circular-shaped ostium. Furthermore, the ostia of ruptured aneurysms tend to have a smaller area, which is also correlated with the aneurysm’s size. While also other variables were significantly correlated, strong linear correlations can only be seen between the area of the ostium with the aneurysm’s volume and surface. Conclusion The proposed shape indices open up new possibilities to quantitatively describe and compare ostia, which can be beneficial for rupture risk assessment and subsequent treatment decision. Additionally, this work shows that the ostium area and the size of the aneurysm are correlated. Further longitudinal studies are necessary to analyze whether stable and unstable aneurysms can be distinguished by their ostia.

The effectiveness of osteopathic treatment 2,5–4,5 year-old children with dysarthria

Background. In recent decades, diagnostic and therapeutic procedures related to classical orthopedics, manual medicine and osteopathy have become widespread in Russian clinical medicine. Osteopathy expands the possibilities of diagnosis and treatment of various diseases due to the fact that its methods are not addressed to individual symptoms of the disease, but to violations of the system organization of physiological functions of the body and to establishing cause-and-effect relationships between mechanical damage of human tissues and the development of subsequent pathologies. Currently, the problem of studying the relationship of indicators of the osteopathic status of preschool children having perinatal signs of dysarthria is relevant for osteopathic doctors. Materials and methods. On the basis of the department of osteopathy of the Yaroslav-the-Wise Novgorod State University and the V.L. Andrianov Institute of the osteopathic medicine, a study was conducted aimed at assessing the clinical and physiological parameters of children aged 2.5 to 4.5 years with dysarthria and further substantiating the effectiveness of oteopathic treatment of adverse functional disorders of the brain that affect oral speech. The work used a computer electroencephalograph Mizar. Ultrasound dopplerography of the brain vessels of the subjects using the transcranial dopplerography device EME/Nicolet as well as ultrasound examination of the cervical spine was performed. The materials obtained in the course of the study were subjected to mathematical and statistical processing using the Statistica 6.0 software package, nonparametric (Wilcoxon test) and parametric methods were used with applying the Students t-test to assess the reliability of differences, and correlation analysis was performed to establish the relationship between clinical, physiological and osteopathic indicators in children before and after treatment. Conclusions. The results of the assessment of the clinical and physiological parameters of the subjects allowed us to infer that the osteopathic treatment was effective.

Elastin-Derived Peptides in the Central Nervous System: Friend or Foe

Elastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display incredible resilience and structural stability with long half-life. However, during some physiological and pathophysiological conditions, elastin is prone to proteolytic degradation and, due to the extremely low turnover rate, its degradation is practically an irreversible and irreparable phenomenon. As a result of elastin degradation, new peptides called elastin-derived peptides (EDPs) are formed. A growing body of evidence suggests that these peptides play an important role in the development of age-related vascular disease. They are also detected in the cerebrospinal fluid of healthy people, and their amount increases in patients after ischemic stroke. Recently, elastin-like polypeptides have been reported to induce overproduction of beta-amyloid in a model of Alzheimer's disease. Nevertheless, the role and mechanism of action of EDPs in the nervous system is largely unknown and limited to only a few studies. The article summarizes the current state of knowledge on the role of EDPs in the nervous system.

A novel epigenetic marker, TET2, is identified in the intractable epileptic brain and regulates ABCB1 in the blood-brain barrier

BackgroundDrug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. DNA methylation, an inheritable but reversible epigenetic change, may participate in this complicated regulatory network. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Thus, we aimed to unravel their role in DRE and their function related to the possible refractory factor ABCB1 in a blood-brain barrier (BBB) model.MethodsWe quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain haemorrhage controls (n = 10) by immunochemical staining. TET2 and ABCB1 expression patterns were determined in the temporal cortex and isolated brain capillaries of DRE patients using immunohistological detection and Western blot analysis, respectively. A BBB model constructed with hCMEC/D3 cells was used to verify the demethylation and regulatory effects of TET2 on ABCB1.ResultsTET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed differences in expression. We also discovered that the vascular endothelium of DRE patients has a strong affinity for TET2. ABCB1 and TET2 have identical densities in the DRE temporal cortex, and they both have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In the BBB, TET2 depletion can cause attenuated expression and function of ABCB1, as well as a pattern of higher methylation in CpG islands of the ABCB1 promoter.ConclusionsThrough a cohort study performed on the temporal cortex and brain vessels of DRE patients, we identified a novel epigenetic marker, TET2. Data from experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE and requires further research.