Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut–brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut–brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels.

Aim: To investigate whether the estimation of cerebrospinal fluid (CSF) and brain YKL-40 levels may be used as an efficient biomarker for Parkinson's disease (PD). Methods: Lipopolysaccharides (LPS... Plain language summary Parkinson's disease (PD) is one of the most devastating fast-spreading neurological disorders with a high prevalence and incidence of death. Progress in developing efficient ...

Alzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.