The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

The perfusion change in acute symptomatic hypoglycemic encephalopathy (ASHE) is not well known. We present the perfusion-weighted imaging of a patient with ASHE. The area of diffusion-weighted imaging abnormalities and adjacent normal-appearing white matter showed increased cerebral blood volume and flow, and shortening of time-to-peak.
Blood Volume ; Brain Diseases* ; Humans ; Perfusion ; White Matter

The perfusion change in acute symptomatic hypoglycemic encephalopathy (ASHE) is not well known. We present the perfusion-weighted imaging of a patient with ASHE. The area of diffusion-weighted imaging abnormalities and adjacent normal-appearing white matter showed increased cerebral blood volume and flow, and shortening of time-to-peak.
Blood Volume ; Brain Diseases* ; Humans ; Perfusion ; White Matter

Brain disease is one of the greatest threats to public health. Brain theranostics is recently taking shape, indicating the treatments of stroke, inflammatory brain disorders, psychiatric diseases, neurodevelopmental disease, and neurodegenerative disease. However, several factors, such as lack of endophenotype classification, blood-brain barrier (BBB), target determination, ignorance of biodistribution after administration, and complex intercellular communication between brain cells, make brain theranostics application difficult, especially when it comes to clinical application. So, a more thorough understanding of each aspect is needed. In this review, we focus on recent studies regarding the role of exosomes in intercellular communication of brain cells, therapeutic effect of graphene quantum dots, transcriptomics/epitranscriptomics approach for target selection, and in vitro/in vivo considerations.
Blood-Brain Barrier ; Brain Diseases ; Brain ; Classification ; Endophenotypes ; Exosomes ; Graphite ; Neurodegenerative Diseases ; Public Health ; Quantum Dots ; Stroke ; Theranostic Nanomedicine

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
Blood-Brain Barrier ; Brain ; Central Nervous System Diseases ; Humans ; Medicine, Tibetan Traditional ; Stroke/drug therapy*

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
Humans ; Medicine, Chinese Traditional ; Neurodegenerative Diseases/drug therapy* ; Brain ; Aging ; Neurons ; Blood-Brain Barrier

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer’s disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.
Aging ; Amyotrophic Lateral Sclerosis ; Atherosclerosis ; Blood Circulation ; Blood-Brain Barrier ; Brain ; Cholesterol ; Metabolism ; Mitochondria ; Neurodegenerative Diseases ; Parkinson Disease

Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood-brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction.
Blood-Brain Barrier ; Brain ; Central Nervous System ; Immune System* ; Immunotherapy ; Nervous System Diseases* ; Testis ; Urinary Bladder, Neurogenic ; Urologic Diseases ; Urology*

B-type natriuretic peptide (BNP) is a plasma marker of left ventricular dysfunction and cardiac volume overload. Currently it is mainly used in the cardiovascular field. BNP is an intrinsic regulator of the embryonic stem cell proliferation, and the reduction in BNP can increase the apoptosis rate. The epitope of N terminal pro-brain natriuretic peptide-BNP is most stable. BNP1-32 has the strongest biological activity but with lower plasma level in heart failure patients. The plasma BNP level plays an important role in the diagnosis, prognosis, hospital admission and mortality of heart failure, and can be used as a monitoring indicator in the treatment of heart failure. The deficiency of corin enzyme in patients with heart failure can cause the increase of cracking pro-BNP. BNP can also provide diagnostic and prognostic information for other populations and diseases. Genetic studies on BNP and its receptors also provide important information. Nesiritide, neutral endopeptidase inhibitors, and vasopeptidase inhibitors of the natriuretic peptide synthesis have been used for the treatment of cardiovascular disorders. However, more reliable and accurate approaches for detecting BNP and N terminal pro-brain natriuretic peptide-BNP require further investigations.
Cardiovascular Diseases ; blood ; diagnosis ; drug therapy ; Humans ; Natriuretic Peptide, Brain ; blood ; physiology ; therapeutic use

OBJECTIVETo determine the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and evaluate their relationships with cardiac structure and function and liver function in patients with cirrhosis.

METHODSFifty patients with cirrhosis underwent two-dimensional Doppler echocardiography. The cirrhotic patients were divided into groups according to Child-Pugh score:Child-Pugh class A, n=15; Child-Pugh class B, n=20; Child-Pugh class C, n=15. Cardiac dimensions and left and right ventricular functions were evaluated. In addition, the plasma NT-proBNP was detected in the 50 cirrhotic patients and 11 healthy controls.

RESULTSThe levels of plasma NT-proBNP was significantly higher in cirrhotic patients than in healthy controls (240.15+/-80.87 pg/mL vs.55.86+/-20.13 pg/mL, P=0.000).The Child-Pugh class A, B and C groups showed no differences for left ventricular diameter, right ventricular diameter, septal thickness, left ventricular wall thickness, E wave, A wave, aortic annulus diameter, and the value of E/A.However, the left atrial diameter was significantly lower in the A group than in the C group (29.83+/-3.76 mm vs.35.08+/-3.68 mm, P=0.015) and in the B group than in the C group (31.78+/-4.05 mm vs.35.08+/-3.68 mm, P=0.000); there was no significant difference between the A and B groups. The plasma NT-proBNP was significantly lower in the A group than the C group (189.20+/-20.25 pg/mL vs.300.13+/-34.96 pg/mL, P=0.000) and in the B group than in the C group (202.34+/-31.20 pg/mL vs.300.13+/-34.96 pg/mL, P=0.000); there was no significant difference between the A and B groups (P=0.302).The NT-proBNP level was positively correlated with the left atrial diameter and the left ventricular wall thickness (r=0.540, P=0.000 andr=0.309, P=0.029 respectively).In addition, the NT-proBNP showed correlation with Child-Turcotte-Pugh score (r=0.454, P=0.001), albumin level (r=-0.376, P=0.007) and total bilirubin level (r=0.283, P=0.047).

CONCLUSIONs Increased levels of plasma NT-proBNP are related to disease severity in patients with cirrhosis.Furthermore, cardiac dysfunction in patients with cirrhosis may be related to increased plasma levels of NT-proBNP.

Heart Diseases ; complications ; Humans ; Liver Cirrhosis ; complications ; physiopathology ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood