Treatment Of Central Nervous System Diseases Research Articles

PECULIARITIES OF FATAL CASES IN HIV-INFECTED PATIENTS WITH CENTRAL NERVOUS SYSTEM LESIONS IN TUBERCULOSIS INPATIENT SETTINGS FOR 2014-2023

Aim of the work is to study the peculiarities of fatal cases of CNS lesions in patients with tuberculosis against the background of HIV infection.Materials and methods. A retrospective analysis of 68 medical histories of tuberculosis patients with HIV infection who died in the CNE "Zaporizhia Regional Phthisiopulmonology Clinical Treatment and Diagnostic Center" for the years 2014-2023 was carried out. An analysis of the anamnesis, clinical and radiological data, laboratory indicators, final clinical and pathological diagnoses was carried out.Results. The mortality rate among HIV-infected people in TB hospitals has a steady downward trend. In 2014-2023, 1234 patients with HIV infection were treated at the CNE "Zaporizhia Regional Phthisiopulmonology Clinical Treatment and Diagnostic Center", 214 (17.3%) died. In 2014, 33 (24.6%) out of 134 HIV-positive patients died, and in 2023, 3 (6.8%) out of 44 HIV-positive patients died. Central nervous system (CNS) lesions among the dead were noted in 68 (31.8%) patients. The study of medical records found that among those who died with CNS lesions, men prevailed - 55 (80.9%), women - 13 (19.1%), young patients - 53 (77.9%), and 15 (22.1%) patients over 45 years of age. In the structure of central nervous system lesions in patients with active tuberculosis, tuberculous meningoencephalitis prevails in fatal cases - 35 (51.5%), a significant share of cryptococcal meningoencephalitis - 18 (26.5%) and progressive multifocal leukoencephalopathy - 9 (13.2%). The main reason that leads to fatal consequences is the late diagnosis of HIV infection - in 26 (38.2%) the number of CD4<50 cl./μl, 36 (52.9%) patients did not receive antiretroviral therapy (ART), 18 (26 .5%) of patients had been taking ART for a year. Improvement of tuberculosis microbiological diagnosis due to the introduction of the Xpert MTB/RIF® (Ultra) test at all levels of the laboratory network, the introduction of a mandatory test for cryptococci, free CT, MRI examination for the diagnosis in HIV-infected patients, improvement of drug-resistant tuberculosis treatment regimens contributed to the reduction of mortality in case of HIV and tuberculosis combination, which was 24.6% in 2014, and 6.8% in 2023.Conclusions. Diagnosis and treatment of CNS diseases in patients with active tuberculosis against the background of HIV infection requires a comprehensive approach: early diagnosis of HIV infection, tuberculosis and lesions of the CNS, improvement of treatment.

Phenolic-enabled nanotechnology: a new strategy for central nervous system disease therapy.

Polyphenolic compounds have received tremendous attention in biomedicine because of their good biocompatibility and unique physicochemical properties. In recent years, phenolic-enabled nanotechnology (PEN) has become a hotspot of research in the medical field, and many promising studies have been reported, especially in the application of central nervous system (CNS) diseases. Polyphenolic compounds have superior anti-inflammatory and antioxidant properties, and can easily cross the blood‒brain barrier, as well as protect the nervous system from metabolic damage and promote learning and cognitive functions. However, although great advances have been made in this field, a comprehensive review regarding PEN-based nanomaterials for CNS therapy is lacking. A systematic summary of the basic mechanisms and synthetic strategies of PEN-based nanomaterials is beneficial for meeting the demand for the further development of novel treatments for CNS diseases. This review systematically introduces the fundamental physicochemical properties of PEN-based nanomaterials and their applications in the treatment of CNS diseases. We first describe the different ways in which polyphenols interact with other substances to form high-quality products with controlled sizes, shapes, compositions, and surface chemistry and functions. The application of PEN-based nanomaterials in the treatment of CNS diseases is then described, which provides a reference for subsequent research on the treatment of CNS diseases.

Gaining insights into the physicochemical properties and sequence space of blood–brain barrier penetrating peptides

The blood–brain barrier (BBB) poses a significant obstacle to the administration of drugs to the brain for the development of therapies of central nervous system (CNS) disorders. Blood-brain barrier penetrating peptides (BBBPps) are a group of peptides that can traverse the BBB by different processes without causing harm to the BBB. These peptides show promise as potential drugs for CNS ailments. Nevertheless, the process of identifying BBBPps using experimental approaches is both time-consuming and labour-intensive. To discover additional BBBPps as potential treatments for CNS diseases, it is critical to develop insilico methods that can distinguish BBBPps from non- BBBPps rapidly and precisely. In the current work, machine learning aided models are developed for accurate prediction of BBBPps using physicochemical and evolutionary information. The best model achieved an accuracy of 84.8 % by using 5-fold cross-validation and 79.8 % based on the holdout testing set on a reduced set of features. Further an extensive analysis is carried out for the black box models using model agnostic interpretation approaches to infer the physicochemical and sequence space of BBBPps. Basic amino acids and conservation of Arginine and Lysine are found to be more favoured in BBBPps. Further, basic amino acid property group and its interactions with other features are found to be prominent important interactions.

Advancements in the Controlled Delivery of Nanodrugs to the Central Nervous System: Challenges and Innovations.

About 1 million of the 6.8 million deaths attributed to disorders of the central nervous system (CNS) each year are caused by neurodegenerative diseases, which include Parkinson’s disease, Alzheimer’s disease, tumors, and ischemic stroke. Because of the complexity of the brain, CNS issues are a major concern. To address issues with toxicity, specificity, and delivery, several drugs are available to treat illnesses of the central nervous system (CNS). Therapeutic drugs are challenged by barriers such as the blood-brain barrier (BBB), which prevents them from reaching their intended target. Scholars have been investigating pathways for pharmaceuticals to cross the blood-brain barrier and reach their intended targets. These issues show how different cellular processes must be changed or manipulated by nanotechnology to obtain the required properties. Nanoparticles are an efficient replacement for drug delivery and other methods because of their nano size, which allows them to cross the blood-brain barrier. Effective drug transfer and enhanced CNS disease treatment and diagnosis are possible using nanotechnology. Drugs could be altered via nanoengineering to carry out tasks like transferring across the blood-brain barrier, modifying signaling pathways, focusing on certain cells, facilitating efficient gene transfer, and encouraging nerve cell regeneration and preservation.

Tailored Borneol-Modified Lipid Nanoparticles Nasal Spray for Enhanced Nose-to-Brain Delivery to Central Nervous System Diseases.

The nanodrug delivery system-based nasal spray (NDDS-NS) can bypass the blood-brain barrier and deliver drugs directly to the brain, offering unparalleled advantages in the treatment of central nervous system (CNS) diseases. However, the current design of NNDS-NS is excessively focused on mucosal absorption while neglecting the impact of nasal deposition on nose-to-brain drug delivery, resulting in an unsatisfactory nose-to-brain delivery efficiency. In this study, the effect of the dispersion medium viscosity on nasal drug deposition and nose-to-brain delivery in NDDS-NS was elucidated. The optimized formulation F5 (39.36 mPa·s) demonstrated significantly higher olfactory deposition fraction (ODF) of 23.58%, and a strong correlation between ODF and intracerebral drug delivery (R2 = 0.7755) was observed. Building upon this understanding, a borneol-modified lipid nanoparticle nasal spray (BLNP-NS) that combined both nasal deposition and mucosal absorption was designed for efficient nose-to-brain delivery. BLNP-NS exhibited an accelerated onset of action and enhanced brain targeting efficiency, which could be attributed to borneol modification facilitating the opening of tight junction channels. Furthermore, BLNP-NS showed superiority in a chronic migraine rat model. It not only provided rapid relief of migraine symptoms but also reversed neuroinflammation-induced hyperalgesia. The results revealed that borneol modification could induce the polarization of microglia, regulate the neuroinflammatory microenvironment, and repair the neuronal damage caused by neuroinflammation. This study highlights the impact of dispersion medium viscosity on the nose-to-brain delivery process of NDDS-NS and serves as a bridge between the formulation development and clinical transformation of NDDS-NS for the treatment of CNS diseases.

The role of gastrodin in the management of CNS-related diseases: Underlying mechanisms to therapeutic perspectives.

Central nervous system (CNS)-related diseases have a high mortality rate, are a serious threat to physical and mental health, and have always been an important area of research. Gastrodin, the main active metabolite of Gastrodia elata Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti-neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case-control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS-related disorders. However, important concerns need to be addressed in the context of likely non-specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High-quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.

Advanced Noninvasive Strategies for the Brain Delivery of Therapeutic Proteins and Peptides.

Recent years have witnessed rapid progress in the discovery of therapeutic proteins and peptides for the treatment of central nervous system (CNS) diseases. However, their clinical applications have been considerably hindered by challenges such as low biomembrane permeability, poor stability, short circulation time, and the formidable blood-brain barrier (BBB). Recently, substantial improvements have been made in understanding the dynamics of the BBB and developing efficient approaches for delivering proteins and peptides to the CNS, especially by using various nanoparticles. Herein, we present an overview of the up-to-date understanding of the BBB under physiological and pathological conditions, emphasizing their effects on brain drug delivery. We summarize advanced strategies and elucidate the underlying mechanisms for delivering proteins and peptides to the brain. We highlight the developments and applications of nanocarriers in treating CNS diseases via BBB crossing. We also provide critical opinions on the limitations and obstacles of the current strategies and put forward prospects for future research.

Small Scale, Big Impact: Nanotechnology-Enhanced Drug Delivery for Brain Diseases.

Central nervous system (CNS) diseases, ranging from brain cancers to neurodegenerative disorders like dementia and acute conditions such as strokes, have been heavily burdening healthcare and have a direct impact on patient quality of life. A significant hurdle in developing effective treatments is the presence of the blood-brain barrier (BBB), a highly selective barrier that prevents most drugs from reaching the brain. The tight junctions and adherens junctions between the endothelial cells and various receptors expressed on the cells make the BBB form a nonfenestrated and highly selective structure that is crucial for brain homeostasis but complicates drug delivery. Nanotechnology offers a novel pathway to circumvent this barrier, with nanoparticles engineered to ferry drugs across the BBB, protect drugs from degradation, and deliver medications to the designated area. After years of development, nanoparticle optimization, including sizes, shapes, surface modifications, and targeting ligands, can enable nanomaterials tailored to specific brain drug delivery settings. Moreover, smart nano drug delivery systems can respond to endogenous and exogenous stimuli that control subsequent drug release. Here, we address the importance of the BBB in brain disease treatment, summarize different delivery routes for brain drug delivery, discuss the cutting-edge nanotechnology-based strategies for brain drug delivery, and further offer valuable insights into how these innovations in nanoparticle technology could revolutionize the treatment of CNS diseases, presenting a promising avenue for noninvasive, targeted therapeutic interventions.

Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.

Macrocyclic drugs can address an increasing range of molecular targets but enabling central nervous system (CNS) access to these drugs has been viewed as an intractable problem. We designed and synthesized a series of quinolinium-modified cyclosporine derivatives targeted to the mitochondrial cyclophilin D protein. Modification of the cation to enable greater delocalization was confirmed by x-ray crystallography of the cations. Critically, greater delocalization improved brain concentrations. Assessment of the compounds in preclinical assays and for pharmacokinetics identified a molecule JP1-138 with at least 20 times the brain levels of a non-delocalized compound or those reported for cyclosporine. Levels were maintained over 24 hours together with low hERG potential. The paradigm outlined here could have widespread utility in the treatment of CNS diseases.

Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood-brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods-such as intravenous, intrathecal, and intraparenchymal routes-and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.

Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood‐brain barrier

AbstractThe blood‐brain barrier (BBB) poses daunting challenges in treating diseases associated with the central nervous system (CNS). Recently, the traditional notion of the absence of the lymphatic system in the brain is evolving. The discovery of the glymphatic system in the brain has stimulated tremendous interest in developing new strategies for the treatment of CNS diseases. Leveraging the glymphatic system for CNS drug delivery may pave a new avenue to circumvent the BBB and achieve efficient drug delivery. The review focuses on the glymphatic system of the brain, discussing potential factors affecting its functions and exploring their connections with the meningeal lymphatic system. Finally, the review provides an overview of the drug delivery methods through the glymphatic system to circumvent BBB and regulate brain immunity. These innovative drug delivery methods may significantly improve drug utilization and create new avenues for the treatment of brain diseases.

Minimally invasive nasal infusion (MINI) approach for CNS delivery of protein therapeutics: A case study with ovalbumin

One of the primary obstacles in treating central nervous system (CNS) disorders lies in the limited ability of disease-modifying drugs to cross the blood-brain barrier (BBB). Our previously described Minimally Invasive Nasal Depot (MIND) technique has proven successful in delivering various drugs to the brain in rat models via a trans-olfactory mucosal approach. In this study, we introduce a novel Minimally Invasive Nasal Infusion (MINI) delivery approach for administering ovalbumin, a model protein, utilizing a programmable infusion pump (iPRECIO SMP-310R) in a mouse model. This research highlights the significant role of olfactory mucosa in nose-to-brain delivery, with an efficacy of nearly 45% compared to intracerebroventricular (ICV) administration. This demonstrates its potential as an alternative procedure for treating CNS diseases, offering a greater safety profile relative to the highly invasive clinical routes traditionally adopted for CNS drug delivery.

Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.

Phosphodiesterases (PDE) are involved in the regulation of cellular physiological processes and neurological functions, including neuronal plasticity, synapto-genesis, synaptic transmission, memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system (CNS) diseases by inhibiting cAMP hydrolysis, increasing cAMP content and enhancing its downstream effects. PDE4 inhibitors have long-term potentiation effect, which can enhance phosphorylation of cAMP response element binding protein (CREB) and upregulate expression of memory related Arc genes in hippocampal neurons, thereby improving cognitive impairment and Alzheimer's disease-like symptoms. They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell functions. Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders, therefore it is considered as a therapeutic target for schizophrenia. PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor (RAGE), TLR4 and NLRP3 pathways in the hippocampus, reducing the activation of microglia and the production of IL-1β, down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors. PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells, increasing nociceptive threshold, and improving mutual learning and memory deficits. PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein (FMRP). PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination, which has potential in the treatment of multiple sclerosis. PDE4 is also related to bipolar disorder, which may be one of the therapeutic targets. At present, several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases. This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases, providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.

Progresses in the establishment, evaluation, and application of invitro blood-brain barrier models.

The blood-brain barrier (BBB) is a barrier between the circulatory system and the central nervous system (CNS), contributing to CNS protection and maintaining the brain homeostasis. Establishment of invitro BBB models that are closer to the microenvironment of the human brain is helpful for evaluating the potential and efficiency of a drug penetrating BBB and thus the clinical application value of the drug. The invitro BBB models not only provide great convenience for screening new drugs that can access to CNS but also help people to have a deeper study on the mechanism of substances entering and leaving the brain, which makes people have greater opportunities in the treatment of CNS diseases. Up to now, although much effort has been paid to the researches on the invitro BBB models and many progresses have been achieved, no unified method has been described for establishing a BBB model and there is much work to do and many challenges to be faced with in the future. This review summarizes the research progresses in the establishment, evaluation, and application of invitro BBB models.

Brain Delivery of Protein Therapeutics by Cell Matrix-Inspired Biomimetic Nanocarrier.

Protein therapeutics are anticipated to offer significant treatment options for central nervous system (CNS) diseases. However, the majority of proteins are unable to traverse the blood-brain barrier (BBB) and reach their CNS target sites. Inspired by the natural environment of active proteins, the cell matrix components hyaluronic acid (HA) and protamine (PRTM) are used to self-assemble with proteins to form a protein-loaded biomimetic core and then incorporated into ApoE3-reconstituted high-density lipoprotein (rHDL) to form a protein-loaded biomimetic nanocarrier (Protein-HA-PRTM-rHDL). This cell matrix-inspired biomimetic nanocarrier facilitates the penetration of protein therapeutics across the BBB and enables their access to intracellular target sites. Specifically, CAT-HA-PRTM-rHDL facilitates rapid intracellular delivery and release of catalase (CAT) via macropinocytosis-activated membrane fusion, resulting in improved spatial learning and memory in traumatic brain injury (TBI) model mice (significantly reduces the latency of TBI mice and doubles the number of crossing platforms), and enhances motor function and prolongs survival in amyotrophic lateral sclerosis (ALS) model mice (extended the median survival of ALS mice by more than 10 days). Collectively, this cell matrix-inspired nanoplatform enables the efficient CNS delivery of protein therapeutics and provides a novel approach for the treatment of CNS diseases.

Delivery of Chlorambucil to the Brain Using Surface Modified Solid Lipid Nanoparticles.

The delivery of drugs to the brain in the therapy of diseases of the central nervous system (CNS) remains a continuing challenge because of the lack of delivery systems that can cross the blood-brain barrier (BBB). Therefore, there is a need to develop an innovative delivery method for the treatment of CNS diseases. Thus, we have investigated the interaction of γ-aminobutyric acid (GABA) and S-(-)-γ-amino-α-hydroxybutyric acid (GAHBA) with the GABA receptor by performing a docking study. Both GABA and GAHBA show comparable binding affinities toward the receptor. In this study, we developed surface-modified solid lipid nanoparticles (SLNs) using GAHBA-derived lipids that can cross the BBB. CLB-loaded SLNs were characterized by a number of methods including differential scanning calorimetry, dynamic light scattering, UV-vis spectroscopy, and transmission electron microscopy. The blank and CLB-loaded SLN suspensions were found to exhibit good storage stability. Also, the SLNs showed a higher encapsulation efficiency for CLB drugs. In vitro release kinetics of CLB at physiological temperature was also investigated. The results of the in vitro cell cytotoxicity assay and flow cytometry studies in the human glioma U87MG cell line and human prostate cancer PC3 cell line suggested a higher efficacy of the GAHBA-modified CLB-loaded SLNs in U87MG cells. The transcription level of GABA receptor expression in the target organ and cell line was analyzed by a reverse transcription polymerase chain reaction study. The in vivo biodistribution and brain uptake in C57BL6 mice and SPECT/CT imaging in Wistar rats investigated using 99mTc-labeled SLN and autoradiography suggest that the SLNs have an increasing brain uptake. We have demonstrated the delivery of the anticancer drug chlorambucil (CLB) to glioma.

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord

BackgroundMechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood.MethodsSpinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery.ResultsSpinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI.ConclusionsWe reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

Swimming short fibrous nasal drops achieving intraventricular administration

Adequate drug delivery across the blood–brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Isolation and usage of exosomes in central nervous system diseases.

Exosomes are vesicles secreted by all types of mammalian cells. They are characterized by a double-layered lipid membrane structure. They serve as carriers for a plethora of signal molecules, including DNA, RNA, proteins, and lipids. Their unique capability of effortlessly crossing the blood-brain barrier underscores their critical role in the progression of various neurological disorders. This includes, but is not limited to, diseases such as Alzheimer's, Parkinson's, and ischemic stroke. Establishing stable and mature methods for isolating exosomes is a prerequisite for the study of exosomes and their biomedical significance. The extraction technologies of exosomes include differential centrifugation, density gradient centrifugation, size exclusion chromatography, ultrafiltration, polymer coprecipitation, immunoaffinity capture, microfluidic, and so forth. Each extraction technology has its own advantages and disadvantages, and the extraction standards of exosomes have not been unified internationally. This review aimed to showcase the recent advancements in exosome isolation techniques and thoroughly compare the advantages and disadvantages of different methods. Furthermore, the significant research progress made in using exosomes for diagnosing and treating central nervous system (CNS) diseases has been emphasized. The varying isolation methods result in differences in the concentration, purity, and size of exosomes. The efficient separation of exosomes facilitates their widespread application, particularly in the diagnosis and treatment of CNS diseases.

Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is widely used in clinical practice to treat diseases related to central nervous system (CNS) damage. However, the blood-brain barrier (BBB) constitutes a significant impediment to the effective delivery of TCM, thus substantially diminishing its efficacy. Advances in nanotechnology and its applications in TCM (also known as nano-TCM) can deliver active ingredients or components of TCM across the BBB to the targeted brain region. This review provides an overview of the physiological and pathological mechanisms of the BBB and systematically classifies the common TCM used to treat CNS diseases and types of nanocarriers that effectively deliver TCM to the brain. Additionally, drug delivery strategies for nano-TCMs that utilize in vivo physiological properties or in vitro devices to bypass or cross the BBB are discussed. This review further focuses on the application of nano-TCMs in the treatment of various CNS diseases. Finally, this article anticipates a design strategy for nano-TCMs with higher delivery efficiency and probes their application potential in treating a wider range of CNS diseases.