Search results for "Protective Agent"
showing 10 items of 226 documents
Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection.
2017
Dimethyl fumarate (DMF) is an immunomodulatory compound to treat multiple sclerosis and psoriasis with neuroprotective potential. Its mechanism of action involves activation of the antioxidant pathway regulator Nuclear factor erythroid 2-related factor 2 thereby increasing synthesis of the cellular antioxidant glutathione (GSH). The objective of this study was to investigate whether post-traumatic DMF treatment is beneficial after experimental traumatic brain injury (TBI). Adult C57Bl/6 mice were subjected to controlled cortical impact followed by oral administration of DMF (80 mg/kg body weight) or vehicle at 3, 24, 48, and 72 h after the inflicted TBI. At 4 days after lesion (dal), DMF-tr…
Uric acid treatment after stroke modulates the Krüppel-like factor 2-VEGF-A axis to protect brain endothelial cell functions: Impact of hypertension
2019
Uric acid (UA) is a promising protective treatment in ischaemic stroke, but the precise molecular targets underlying its in vivo beneficial actions remain unclear. High concentrations of UA inhibit angiogenesis of cultured endothelial cells via Krüppel-like factor 2 (KLF)-induced downregulation of vascular endothelial growth factor (VEGF), a pro-angiogenic mediator that is able to increase blood–brain barrier (BBB) permeability in acute stroke. Here, we investigated whether UA treatment after ischaemic stroke protects brain endothelial cell functions and modulates the KLF2-VEGF-A axis. Transient intraluminal middle cerebral artery (MCA) occlusion/reperfusion was induced in adult male sponta…
Neuroprotective potential of antihyperglycemic drug metformin in streptozocin-induced rat model of sporadic Alzheimer's disease.
2020
Abstract The earliest hallmarks of sporadic Alzheimer's disease (sAD) are impaired glucose metabolism, chronic neuroinflammation, diminished synaptic plasticity and subsequent cognitive decline. The safest antidiabetic drug metformin has shown both glucose metabolism-improving and cognition-enhancing action in type 2 diabetes patients and diabetic model animals. However, metformin has not been previously studied in intracerebroventricular streptozocin (STZ)-induced model of sAD. Therefore, our aim was to assess the preventive action of metformin in sAD model-rats. Firstly, the actions of metformin (75 and 100 mg/kg) on cognitive functions and sociability were examined. Secondly, we wanted t…
GABA-containing compound gammapyrone protects against brain impairments in Alzheimer's disease model male rats and prevents mitochondrial dysfunction…
2018
Neuroinflammation, oxidative stress, decreased glucose/energy metabolism, and disrupted neurotransmission are changes that occur early in sporadic Alzheimer's disease (AD), manifesting as mild cognitive impairment. Recently, the imbalanced function of the gamma-aminobutyric acid (GABA) system was identified as a critical factor in AD progression. Thus, maintaining balance among neurotransmitter systems, particularly the GABA system, can be considered a beneficial strategy to slow AD progression. The present study investigated the effects of the compound gammapyrone, a molecule containing three GABA moieties: "free" moiety attached to the position 4 of the 1,4-dihydropyridine (DHP) ring, and…
Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain.
2018
Growing evidence suggests a link between obesity and neurodegeneration. The purpose of the present study was to explore the neuroprotective potential of glucagon-like peptide-2 (GLP-2) in the brain of high fat diet (HFD)-fed mice. Markers of inflammation and oxidative stress were analysed in the brains of obese mice chronically treated with [Gly2]-GLP-2 (teduglutide), the stable analogue of the GLP-2, and they were compared to age-matched untreated obese and lean animals. Neurodegeneration was examined by TUNEL assay. HFD feeding increased the expression of pro-inflammatory mediators (NF-kB, IL-8, TNF-α, IL-1β and IL-6), glial fibrillary acidic protein (GFAP), index of gliosis and neurodege…
Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats.
2018
Preclinical and clinical studies support a promising, albeit not definitive, neuroprotective effect of emergent uric acid (UA) administration in ischemic stroke. We assessed the effects of UA in an ischemic stroke model relevant to the current treatment paradigm of mechanical thrombectomy within the STAIR/RIGOR recommendations. A cohort of male and female Wistar rats was subjected to ischemic stroke with mechanical recanalization under physiological monitoring. The effects of transient middle cerebral artery occlusion (tMCAO) with adjunctive UA (IV, 16 mg/kg) or vehicle treatment were assessed at 24 h and 7 days. Outcomes included neurofunctional impairment, brain infarct (TTC staining, MRI…
Recombinant human hepatocyte growth factor provides protective effects in cerulein-induced acute pancreatitis in mice.
2018
Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8 hourly administrations of supramaximal cerulein injections (50 µg/kg, ip…
Radioprotection and Radiomitigation: From the Bench to Clinical Practice.
2020
The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by …
Neurodegenerative diseases: Might citrus flavonoids play a protective role?
2016
Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay th…
Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases
2017
When thinking about neurodegenerative diseases, the first symptoms that come to mind are loss of memory and learning capabilities, which all resemble hallmarks of manifestation of such diseases in the central nervous system (CNS). However, the gut comprises the largest nervous system outside the CNS that is autonomously active and in close interplay with its microbiota. Therefore, the enteric nervous system (ENS) might serve as an indicator of degenerative pathomechanisms that also affect the CNS. On the other hand, it might offer an entry point for devastating influences from the microbial community or – conversely – for therapeutic approaches via gut commensals. Within the last years, the…