Increasing evidence suggests seizures cause blood–brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3–15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood–brain barrier permeability. We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.

Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden.

Background: Mental disorders are the leading cause of global non-fatal disease burden, with rising prevalence among children, adolescents, and youth. This study analyzed location-, age-, and sex-specific estimates for nine mental disorders from 1990 to 2021 using GBD 2021 data, projecting burden to 2050.Methods: Methods included calculating average annual percentage change (AAPC) and annual percentage change (APC) for age-standardized prevalence rate (ASPR) and disability-adjusted life years rate (ASDR), alongside decomposition, inequality, frontier, comparative risk, and Bayesian age-period-cohort analyses.Results: Compared to 1990, the 2021 global burden significantly increased among youth [the AAPC of ASPR = 0.15, 95% confidence interval (CI): 0.14 to 0.16; the AAPC of ASDR = 0.40, 95% CI: 0.29 to 0.51], accelerating sharply after 2019 (the APC of ASPR = 4.74, 95% CI 4.55 to 4.93; the APC of ASDR = 6.64, 95% CI 4.88 to 8.42). Males experienced a higher burden than females, with variations in sex-specific patterns across age groups. Burden varied substantially by socio-demographic index (SDI), being highest in high-SDI regions [ASPR = 12913.13, 95% uncertainty interval (UI): 11135.82 to 14874.98; ASDR = 1750.41, 95% UI: 1253.46 to 2328.87]. We found that the burden changes of nine mental disorders vary at the global, regional, and national levels. Decomposition analysis highlighted that the changes in prevalence and the disability-adjusted life years (DALYs) were predominantly driven by population growth (84.86% and 57.92%), with the most significant improvements observed in higher SDI regions. Frontier analysis revealed the potential for burden reduction in higher income countries and territories. Globally, key risk factors included childhood sexual abuse, bullying, intimate partner violence, and lead exposure were identified for anxiety disorders, depressive disorders, and idiopathic developmental intellectual disability, respectively. Projections indicated that the burden of mental disorders is likely to continue its decline in 2050 (ASPR = 6120.71 per 100,000, 95% CI: 3973.57 to 8267.85; ASDR = 844.71 per 100,000, 95% CI: 529.48 to 1159.94).Conclusion: Despite projected rate declines by 2050, the global burden of mental disorders is increasing, with significant disparities across populations and a recent surge demanding intensified prevention and equitable healthcare expansion worldwide.

A one-step synthesis of phloretin derivatives 2–11 from phloretin in good to excellent yields is reported. Their structures were characterized by ¹H-NMR, ¹³C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A mechanism for the formation of 9–11 is proposed. Compared with the anticancer drug docetaxel, phloretin, phloretin derivatives and phlorizin exhibited moderate cytotoxicity toward the MDA-MB-231, SPC-A1, A549, MCF-7 and EC109 cell lines. Among all of the tested compounds, 7 exhibited the strongest cytotoxicity toward the five cell lines and was more active than docetaxel in MDA-MB-231 cells. Our findings suggest that these derivatives hold great promise for further development as anticancer agents.