Volume 36, Issue 4

Cholecystokinin (CCK) is a major neuropeptide in the brain that functions as a neurotransmitter, hormone, and growth factor. The peptide and its receptors are widely expressed in the brain. CCK signaling modulates synaptic plasticity and can improve or impair memory formation, depending on the brain areas studies and the receptor subtype activated. Studies have shown in a series of animal models of neurodegenerative diseases that CCK receptor agonists show neuroprotective effects and can effectively alleviate oxidative stress, alleviate chronic inflammation of the central nervous system, improve neuronal synaptic plasticity, prevent neuronal loss, and improve cognitive dysfunction in Alzheimer’s disease (AD) model mice and motor activity in animal models of Parkinson’s disease. In addition, CCK plays important roles in the amygdala to regulate anxiety and depressive states. Activation of interneurons or inhibition of excitatory neurons can improve anxiety levels. This review summarizes the effects on memory formation and synaptic plasticity, the neuroprotective effects of cholecystokinin and its analogs in neurological diseases such as Alzheimer and Parkinson’s disease, and the effects on anxiety and neuronal activity in the amygdala.

Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5–1 % of the population, epilepsy remains a serious public health concern. Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to a substantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important. In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy. Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research in this area. This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.

Stroke is a severe neurological disease and a major worldwide issue, mostly manifesting as ischemic stroke (IS). In order to create effective treatments for IS, it is imperative to fully understand the underlying pathologies, as the existing therapeutic choices are inadequate. Recent investigations have shown the complex relationships between several programmed cell death (PCD) pathways, including necroptosis, ferroptosis, and pyroptosis, and their correlation with immune responses during IS. However, this relationship is still unclear. To address this gap, this review study explored the cellular interactions in the immune microenvironment of IS. Then, to validate prior findings and uncover biomarkers, the study investigated bioinformatics studies. Several pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Toll-like receptor 4 (TLR4), and receptor-interacting protein kinase (RIPK), were involved in PCD-immune interactions. The bioinformatics studies reported key biomarkers such as glutathione peroxidase 4 (GPX4), NOD-like receptor family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), and TLR4, which have important implications in ferroptosis, cuproptosis, pyroptosis, and necroptosis respectively. These biomarkers were associated with PCD mechanisms such as oxidative stress and inflammatory reactions. The immune infiltration analysis consistently revealed a significant correlation between PCD pathways and detrimental immune cells, such as neutrophils and γδ T cells. Conversely, M2 macrophages and T helper cells showed protective effects. In conclusion, considering the intricate network of interactions between immune responses and PCD pathways, this study emphasized the necessity of a paradigm shift in therapeutic approaches to address the injuries that are related to this complex network.

Essentially, the blood–brain barrier (BBB) serves as a line of demarcation between neural tissues and the bloodstream. A unique and protective characteristic of the blood–brain barrier is its ability to maintain cerebral homeostasis by regulating the flux of molecules and ions. The inability to uphold proper functioning in any of these constituents leads to the disruption of this specialized multicellular arrangement, consequently fostering neuroinflammation and neurodegeneration. Recent advancements in nanomedicine have been regarded as a promising avenue for improving the delivery of drugs to the central nervous system in the modern era. A major benefit of this innovation is that it allows drugs to accumulate selectively within the cerebral area by circumventing the blood–brain barrier. Although brain-targeted nanomedicines have demonstrated impressive achievements, certain limitations in targeting specificity still exist. In this examination, we scrutinize the distinctive physical and chemical attributes of nanoparticles (NPs) contributing to their facilitation in BBB traversal. We explore the various mechanisms governing NP passage over the BBB, encompassing paracellular conveyance, mediated transport, as well as adsorptive- and receptor-mediated transcytosis. The therapeutic success of NPs for the treatment of brain tumors has been extensively investigated through the use of various categories of NPs. Among these are polymeric nanoparticles, liposomes, solid lipid nanoparticles, dendrimers, metallic nanoparticles, quantum dots, and nanogels. The potential utility of nanoparticles goes beyond their ability to transport pharmaceuticals. They can serve as adept imaging contrast agents, capable of being linked with imaging probes. This will facilitate tumor visualization, delineate lesion boundaries and margins, and monitor drug delivery and treatment response. Versatile nanoparticles can be engineered to effectively target neoplastic lesions, serving dual roles in diagnostic imaging and therapeutic interventions. Subsequently, this discourse explores the constraints associated with nanoparticles in the context of treating brain tumors.

Glioblastoma multiforme (GBM) is the most fatal brain tumor with a poor prognosis with current treatments, mainly because of intrinsic resistance processes. GBM is also referred to as grade 4 astrocytoma, that makes up about 15.4 % of brain cancers globally as well as 60–75 % of astrocytoma. The most prevalent therapeutic choices for GBM comprise surgery in combination with radiotherapy and chemotherapy, providing patients with an average survival of 6–14 months. Nanocarriers provide various benefits such as enhanced drug solubility, biocompatibility, targeted activity, as well as minimized side effects. In addition, GBM treatment comes with several challenges such as the presence of the blood–brain barrier (BBB), blood–brain tumor barrier (BBTB), overexpressed efflux pumps, infiltration, invasion, drug resistance, as well as immune escape due to tumor microenvironment (TME) and cancer stem cells (CSC). Recent research has focused on nanocarriers due to their ability to self-assemble, improve bioavailability, provide controlled release, and penetrate the BBB. These nano-based components could potentially enhance drug accumulation in brain tumor tissues and reduce systemic toxicity, making them a compelling solution for GBM therapy. This review captures the complexities associated with multi-functional nano drug delivery systems (NDDS) in crossing the blood–brain barrier (BBB) and targeting cancer cells. In addition, it presents a succinct overview of various types of targeted multi-functional nano drug delivery system (NDDS) which has exhibited promising value for improving drug delivery to the brain.