Development of cell-based DDS to overcome biological barriers for treating brain diseases

Behavioral Neurology and Neuropsychiatry Fellowship Training: The Johns Hopkins Model

Neurosonography: Shaping the future of neuroprotection strategies in extremely preterm infants

Brain diseases pose a great threat to human health worldwide, thus it is of great importance to explore new materials for their diagnosis and therapy. Compared with the ultraviolet (UV) and visible light, near infrared (NIR) light has better biosafety, lower tissue auto‐fluorescence, and stronger penetration into skull. Hence, NIR light responsive materials have attracted great attention recently which can not only realize the high spatial resolution and signal‐to‐noise ratio imaging for diagnosis, but also achieve effective NIR light triggered treatment noninvasively. Besides, the brain lesions can be visualized clearly by NIR imaging, which can provide more accurate information for guiding treatments. Therefore, this work systematically summarizes the recent advances of NIR light responsive materials for diagnosis and treatment of brain diseases. Firstly, this work briefly reviews the pathological features of blood brain barrier (BBB) and the rational design of materials to target brain disease. Then, the emerging approaches for diagnosis and treatment of various brain diseases with NIR light responsive materials are introduced. Subsequently, the imaging‐guided therapies are elaborated, such as the fluorescence imaging guided surgery and sonodynamic therapy. Finally, some challenges and prospects on the design of NIR light responsive materials for precise diagnosis and therapy of brain diseases are put forward.

Superoxide dismutase (SOD) is an important metalloenzyme that catalyzes the dismutation of superoxide radicals (O2˙-) into hydrogen peroxide (H2O2) and oxygen (O2). However, the clinical application of SOD is severely limited due to its structural instability and high cost. Compared with natural enzymes, nanomaterials with enzyme-like activity, nanoenzymes, are more stable, economical and easy to modify and their activity can be adjusted. Certain nanozymes that exhibit SOD-like activity have been created and shown to help prevent illnesses brought about by oxidative stress. These SOD-like nanozymes offer an important solution to the problems associated with the clinical application of SOD. In this review, we briefly introduce neurodegenerative diseases, present the research progress of SOD-like nanoenzymes in the diagnosis and treatment of brain diseases, review their mechanism of action in the treatment and diagnosis of brain diseases, and discuss the shortcomings of the current research with a view to providing a reference for future research. We expect more highly active SOD-like nanoenzymes to be developed with a wide range of applications in the diagnosis and treatment of brain diseases.

Statins are used for the primary and secondary prevention of cardiovascular disease by inhibiting cholesterol synthesis in the liver. Statins have also noncholesterol-related effects, called pleiotropic effects, which arise from statins' anti-inflammatory, immunomodulatory and antioxidant properties. These effects are especially attractive for the treatment of various brain diseases ranging from stroke to neurodegenerative diseases. Still, low brain concentrations after oral drug administration hinder the clinical application of statins in these pathologies. Pharmaceutical nanotechnologies may offer a solution to this problem, as local or targeted delivery of nanoencapsulated statins may increase brain availability. This special report rapidly summarizes the potential of statins in the treatment of brain diseases and the pharmaceutical nanotechnologies that could provide a viable approach to enable these indications.

The brain is probably the most complex organ in the human body. It has been the hot spot and direction of brain science research all over the world to deeply study the pathogenesis of various kinds of brain diseases and find effective treatment methods. Acupuncture is a nonpharmacological therapy of traditional Chinese medicine originating from ancient clinical practice. The research on the treatment of brain diseases by acupuncture has been constantly enriched and updated with the promotion of interdisciplinary research. In order to account for the current achievements in the field of acupuncture for brain diseases, this article reviews it in terms of conception, application, and exploration. Based on the literature review, we found that in the past decades, acupuncture has received widespread attention worldwide and many literatures have reported the clinical efficacy and underlying mechanisms of acupuncture in the treatment of brain diseases. Presently, the conception, application, and exploration of acupuncture in the treatment of brain diseases have evolved from empirical medicine to evidence-based medicine and precision medicine, and are experiencing a deeper understanding of the information about acupuncture regulating the brain function based on interdisciplinary research.

Activatable luminescent probes for imaging brain diseases

Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.

Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.

Objective To verify the feasibility of remote manipulation of deep brain stimulation (DBS) with 5G communication for the treatment of brain diseases. Methods In March 2019, 3 patients(2 parkinson′s disease and 1 essential tremor) who planned to undergo DBS at Department of Neurosurgery, the First Medical Center of the PLA General Hospital were prospectively recruited into this study. The 5G communication links were established between Beijing and Sanya, Hainan (Hainan Hospital of PLA Gerenal Hospital). The operation group completed the steps such as installation of head frame, craniotomy, microelectrode puncture for the patients in the operation room in Beijing. The remote-control group completed the steps such as remote surgery planning, remote control of microelectrode recording (MER), and imaging results confirmation of electrode implantation. Results During remote surgical procedures under 5G communication, the maximum downlink peak rate was 119 Mbps, the uplink peak rate was 27 Mbs, and the average delay was 76 ms. During the operation, the remote control of the MER drive system ran smoothly and there was no delay of signal transmission. The voice and picture of the operating room and the MER signal were transmitted smoothly. The operation was completed successfully. There were no complications such as puncture bleeding, infection and skin ulceration after the operation. At 3-month follow-up, based on clinical rating scale for tremor (CRST) the score of essential tremor patient was improved by 43.6%; the UPDRS (unified Parkinson disease rating scale)-Ⅲ scores of 2 Parkinson′s disease patients were improved by 84.9% and 90.5% respectively. Conclusion The remote control of MER in DBS surgery with 5G communication seems to have certain feasibility. Key words: Parkinson disease; Essential tremor; Deep brain stimulation; 5G communication; Remote control surgery

Brain is by far the most complex organ in the body. It is involved in the regulation of cognitive, behavioral, and emotional activities. The organ is also a target for many diseases and disorders ranging from injuries to cancers and neurodegenerative diseases. Brain diseases are the main causes of disability and one of the leading causes of deaths. Several drugs that have shown potential in improving brain structure and functioning in animal models face many challenges including the delivery, specificity, and toxicity. For many years, researchers have been facing challenge of developing drugs that can cross the physical (blood–brain barrier), electrical, and chemical barriers of the brain and target the desired region with few adverse events. In recent years, nanotechnology emerged as an important technique for modifying and manipulating different objects at the molecular level to obtain desired features. The technique has proven to be useful in diagnosis as well as treatments of brain diseases and disorders by facilitating the delivery of drugs and improving their efficacy. As the subject is still hot, and new research findings are emerging, it is clear that nanotechnology could upgrade health care systems by providing easy and highly efficient diagnostic and treatment methods. In this review, we will focus on the application of nanotechnology in the diagnosis and treatment of brain diseases and disorders by illuminating the potential of nanoparticles.

The most complex organ in our body is the brain. It also plays a significant role in regulating behavioural, emotional, and cognitive activities. The brain is the target of many ailments, from cancer to neurodegenerative diseases and injuries. Brain diseases refer to a broad group of disease conditions that affect the brain, such as dysfunctions, infections, tumours, injuries, and neurological disorders. In last years, nanotechnology has appeared as an important technique used to obtain materials with desired properties by changing and operating different items at the molecular level. With this feature, nanotechnology has proven to be useful in the diagnosis and medication of brain diseases and disorders by facilitating the distribution of drugs and increasing drug effectiveness. Brain diseases continue to be an important health, economic, and social burden due to high failure rates in transferring therapeutic drugs to the clinic. This chapter discusses the use of various nanoparticles in the diagnosis and treatment of brain diseases, including neurodegenerative disorders, brain tumours, and stroke. There are many promising publications in the literature studying different nanotherapeutics. However, further research on their toxicity and bioaccumulation in clinical settings is required to improve the application of nanotherapeutics in the brain. Thus, the potential of nanomaterials in the treatment of brain diseases and disorders is increased.

Advanced nanoparticle engineering for precision therapeutics of brain diseases.

Brain diseases, including Alzheimer's disease (AD), brain tumors and Parkinson's disease (PD), pose heavy pressure on the public healthcare system. The main obstacle to vanquish brain diseases is the blood-brain barrier (BBB), which is a selective barrier mainly formed by brain endothelial cells. BBB prevents almost all drugs from reaching the brain, thereby hindering drug delivery. Over the past few decades, considerable signs of progress have been made in crossing the BBB and treating brain diseases. Gold nanoparticles (AuNPs) demonstrate the characteristics of adjustable size, unique optical properties, flexible surface modification, and good biocompatibility, which all contribute AuNPs as a promising candidate in biomedical fields. This article reviews the structure and properties of BBB, and discusses main transport routes through the BBB. Besides, nanoparticles, specially AuNPs applied in brain diseases as main drug delivery platforms, are systematically summarized, emphasizing several methods to modify AuNPs, including tuning particle size and surface modification, which are aimed at promoting BBB penetration or prolonging circulation time of AuNPs. In addition, AuNPs utilized in brain diseases are introduced in detail from the aspects of brain imaging, AD, brain tumors, and PD. Prospects and challenges that need to be considered in further investigations and clinical transformation of AuNPs used in brain diseases are also included, hoping to bring new insights into the applications of AuNPs in brain diseases.