Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents

Abstract

Increased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic model is a useful tool to study the link between cerebrovascular pathology and neurodegeneration, while APP–PSEN1 humanized mouse is a model of Alzheimer’s disease. The aim of the current study was to characterize the inflammatory changes in the brain with healthy aging and in neurodegeneration. Also, the cerebro-morphological and cognitive alterations have been investigated. The nose-to-brain delivery of a P-glycoprotein substrate model drug (quinidine) was monitored in the disease models and compared with the age-matched controls. Our results revealed an inflammatory balance shift in both the healthy aged and neurodegenerative models. In normal aging monocyte chemoattractant protein-1, stem cell factor and Rantes were highly upregulated indicating a stimulated leukocyte status. In APOB-100 mice, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), and interleukin-17A (IL-17A) were induced (vascular reaction), while in APP–PSEN1 mice resistin, IL-17A and GM-CSF were mostly upregulated. The nasal drug absorption was similar in the brain and blood indicating the molecular bypass of the BBB. The learning and memory tests showed no difference in the cognitive performance of healthy aged and young animals. Based on these results, it can be concluded that various markers of chronic inflammation are present in healthy aged and diseased animals. In APOB-100 mice, a cerebro-ventricular dilation can also be observed. For development of proper anti-aging and neuroprotective compounds, further studies focusing on the above inflammatory targets are suggested.

Regenerative Effect of Lyophilized Mesenchymal Stem Cells Combined with Platelet-Rich Fibrin in a Skin Wound Model in Geriatric and Young Rats

“…Aging and cellular senescence are characterized by prolonged activation of in ammatory pathways and increased oxidative stress. 29,30 It has been observed…”

Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice

“…For the pharmacokinetic study of OST in rat plasma and cerebrospinal fluid, male Sprague–Dawley rats (SD rats, 300 ± 20 g) were purchased from Guangzhou University of Chinese Medicine Animal Laboratory Center. In order to further address the enhanced pharmacological effects of OST/BO gel with nasal administration, 4-month-old male APP/PS1 transgenic mice ( Varga-Medveczky et al, 2021 ) were purchased from Beijing Hfk Bioscience Co., Ltd. (Beijing, China) (certification number SCXK 2014-0004). A control of 4-month-old male C57BL/6J mice were also bought from Guangzhou University of Chinese Medicine Animal Laboratory Center.…”

Sex-specific changes in protein expression of membrane transporters in the brain cortex of 5xFAD mouse model of Alzheimer’s disease

“…Alzheimer’s disease (AD) remains the leading form of dementia worldwide ( Cahill, 2020 ). AD is not a normal part of aging ( Varga-Medveczky et al, 2021 ; Lau et al, 2023 ). The major hallmarks of AD are represented by formation of the brain extracellular amyloid β (Aβ) plaques together with intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs), resulting in synaptic impairment and inflammation ( Scheltens et al, 2021 ).…”