The brain is rich in fatty acids (FAs), with polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (C22:6n-3, DHA) and arachidonic acid (C20:4n-6, ARA), and the former predominantly stored in the form of phosphatidylcholine, phosphatidyl ethanolamine (PE, diacyl and plasma phospholipid proform), and phosphatidylserine (PS), while the latter is mainly found in ethanolamine phosphoglycerides (EPG) and contributes to constitute most of phosphoglycerides. When required by the body, PUFAs are liberated from membrane phospholipids (either directly or via their metabolites, which are generated by a series of enzymatic reactions) to participate in various cerebral physiological processes. PUFAs and their derivatives play crucial roles in modulating numerous bodily functions, including neuronal signal transmission, neurogenesis, neuroinflammation, and glucose uptake in the brain, thereby sustaining fundamental brain function. Although PUFAs have been implicated in a spectrum of neurological disorders, including acute brain injury (TBI), multiple sclerosis (MS), and neurodegenerative diseases, their role in conditions such as depression, Alzheimer's disease (AD), and Parkinson's disease (PD) is particularly noteworthy. These disorders are closely linked to critical brain functions, including cognition, memory, and inflammatory processes. Given the substantial body of research elucidating the involvement of PUFAs in the pathogenesis and progression of these diseases, this review will specifically concentrate on their impact within these contexts. Graphical Abstract n-3/6 polyunsaturated faty acids (PUFAs) are synthesized by the liver and transported to neurons via the circulatory system. The majority of PUFAs exist in the promoting the differentiation of neural stem cells. Additionally, PUFAs facilitate brain glucose uptake and exert anti-inflammatory effects that influence the progression of neurological disorders such as Alzheimer's disease and Parkinson's disease

In recent years, the incidence of intracerebral hemorrhage (ICH) has been increasing steadily. Environmental factors, such as plastic usage and chemical exposure, have been implicated in exacerbating cerebrovascular disease outcomes, including ICH. Acetyl tributyl citrate (ATBC), a non-phthalate plasticizer, is commonly used in food packaging, medical devices, and children's toys. Due to its high leaching potential from plastic materials, human exposure to ATBC has become increasingly prevalent. Although previous studies have generally reported ATBC as safe for human health, they have primarily focused on high-dose exposures, with limited evidence regarding the safety of environmentally relevant concentrations. This study investigated the effects of medium- to long-term exposure to environmentally relevant concentrations of ATBC. The results showed that ATBC exposure contributed to hematoma enlargement, induced neuronal cell death, and severely impaired intestinal barrier function in ICH mice. ATBC pretreatment reduced neurofilament and axon protein expression and activated the SRC-STAT3-MMPs pathway in BV2 cells in vitro. Based on these medium- to long-term in vivo and in vitro findings, ATBC may be a potential environmental risk factor that worsens the prognosis of ICH. The use of ATBC in consumer products warrants careful reevaluation.

Introduction: Dexmedetomidine, a highly specific α2 agonist, has been extensively utilized in clinical sedation and surgical anesthesia since its introduction in 2000 due to its excellent sympatholytic, sedative, and analgesic effects. This review aimed to identify new approaches for the treatment of patients with brain disorders by thoroughly describing the mechanism of action of dexmedetomidine and examining its neuroprotective effects from the standpoints of basic and clinical research.Methods: The PubMed and Web of Science databases were searched using the keywords dexmedetomidine and related brain diseases, although relevant articles from the last decade were included for detailed summarization and analysis.Results: Dexmedetomidine has shown strong neuroprotective effects, such as protection of the blood‐brain barrier, decreased neuronal death, maintained hemodynamic stability, and reduced postoperative agitation and cognitive dysfunction. Furthermore, dexmedetomidine has been shown to exert various neuroprotective effects, including anti‐inflammatory and antioxidative stress effects, modulation of autophagy, and reduction of apoptosis in cerebral diseases.Conclusions: Dexmedetomidine acts as a neuroprotective agent against brain diseases during all phases of treatment. However, clinical trials with larger sample sizes are required to optimize dosage and dosing strategies.

Temozolomide (TMZ) is the first choice chemotherapy agent against glioblastoma, but the TMZ chemotherapy resistance has restricted the clinical application. Although autophagy is considered an adaptive response for cell survival under the pressure of chemotherapy and associated with chemotherapy resistance, its initiator and the precise molecular mechanism remains unknown. In the present study, it was determined that TMZ increases the transient receptor potential cation channel subfamily C member 5 (TRPC5) protein expression and the basal autophagy level, and the upregulation of autophagy is mediated by TRPC5 in glioma cells. Additionally, knockdown of TRPC5 upregulated the chemotherapy sensitivity in vitro and in vivo. Furthermore, TRPC5-small interfering RNA and pharmacological inhibition indicated that the Ca2+/calmodulin dependent protein kinase beta (CaMKK beta)/AMP-activated protein kinase alpha (AMPK alpha)/mechanistic target of rapamycin kinase (mTOR) pathway mediates cell survival autophagy during TMZ treatment. In addition, TMZ-resistant U87/TMZ cells retained a high basal autophagy level, while silence of TRPC5 expression or inhibition of autophagy reversed TMZ resistance. Thus, the present study revealed that TRPC5, an initiator of autophagy, upregulated TMZ resistance via the CaMKK beta/AMPK alpha/mTOR pathway and this indicated a novel therapeutic site for drug resistance in glioma chemotherapy.

Intracerebral hemorrhage (ICH), a severe cerebrovascular disorder with high mortality, leads to secondary brain injury (SBI) primarily through neuroinflammation and blood-brain barrier (BBB) disruption. Among the pathological cascades, excessive activation of macrophages and the CCR5/JAK1/STAT1/MMPs signaling pathway play pivotal roles in amplifying neuronal damage. Apigenin (API), a natural flavonoid with anti-inflammatory and neuroprotective properties, has emerged as a promising therapeutic candidate to counteract these processes. In this study, we developed apigenin-loaded PLGA nanoparticles functionalized with DSPE-PEG2000-RVG29 and DSPE-PEG2000-folic acid (RVG/FA-NPs@API) to achieve targeted delivery to inflammatory macrophages and investigated their therapeutic effects against SBI after ICH. In a murine ICH model, API administration significantly improved neurological outcomes, reduced cerebral edema, suppressed neuronal apoptosis, and preserved BBB integrity. Mechanistically, API bound covalently to JAK1 at Cys1052, inhibiting its phosphorylation and subsequently downregulating the CCR5/JAK1/STAT1/MMPs cascade. Furthermore, RVG/FA-NPs@API demonstrated excellent stability, efficient brain-targeting, and superior biocompatibility, achieving enhanced therapeutic efficacy compared with free API. These findings highlight a novel strategy for targeted immunomodulation and provide translational insights into nanoparticle-assisted delivery of natural compounds for the treatment of ICH-induced SBI.