To evaluate the neuroprotective effect of nootropic drugs, piracetam and vincamine, on Parkinsonʹs disease (PD) in rats, forty adult male Wistar albino rats were randomized into five equal groups: control, haloperidol-induced PD group, and PD groups orally given piracetam (300 mg/kg/day), vincamine (20 mg/kg/day) or both. Four weeks later, motor performance was assessed by stepping test. Y-maze, forced swimming and olfactory preference tests were done for cognitive and behavioral evaluation. Blood samples were collected for measuring serum glucose, calcium, creatine phosphokinase (CPK) and glial cell-derived neurotrophic factor (GDNF). Thereafter, rats were sacrificed and brains were dissected. Striatal tissue of left hemisphere was isolated and homogenized for assay of dopamine, malondialdehyde (MDA), nitrite/nitrate, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß). Right hemisphere was used for histopathological examination of substantia nigra. Results: Rats of PD group showed bradykinesia, cognitive impairment, depressive-like behavior and hyposmia, reductions in serum calcium and GDNF, and in striatal dopamine, GSH, GPx and SOD, while serum glucose and CPK, and striatal MDA, nitrite/nitrate, IL-1ß and TNF-α were increased, as compared to control.Both drugs improved neurological dysfunction and biochemical parameters, as compared to PD group. The histopathological findings revealed neuro-degeneration and neuro-inflammation in PD group, that improved in treated groups. The piracetam effect was mainly anti-inflammatory, while vincamine was mainly antioxidant. Combined treatment resulted in a more potent amelioration of haloperidol-induced changes. Conclusion: Piracetam and vincamine exhibit neuroprotective activity in haloperidol-induced PD, that is more potent with their combination.

Background Neuroinflammation is a major mechanism in neurodegenerative diseases such as Alzheimer’s disease (AD), which is a major healthcare problem. Notwithstanding of ample researches figured out possible molecular mechanisms underlying the pathophysiology of AD, there is no definitive therapeutics that aid in neuroprotection. Therefore, searching for new agents and potential targets is a critical demand. We aimed to investigate the neuroprotective effect of verapamil (VRP) against lipopolysaccharide (LPS)-induced neuroinflammation in mice and whether the time of VRP administration could affect its efficacy. Methods Forty male albino mice were used and were divided into normal control, LPS only, morning VRP, and evening VRP. Y-maze and pole climbing test were performed as behavioral tests. Hematoxylin and eosin together with Bielschowsky silver staining were done to visualize neuroinflammation and phosphorylated tau protein (pTAU); respectively. Additionally, the state of mitochondria, the levels of microglia-activation markers, inflammatory cytokines, intracellular Ca2+, pTAU, and Ca2+-dependent genes involving Ca2+/ calmodulin dependent kinase II (CAMKII) isoforms, protein kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), with the level of VRP in the brain tissue were measured. Results LPS successfully induced neuroinflammation and hyperphosphorylation of tau protein, which was indicated by elevated levels of microglia markers, inflammatory cytokines, and intracellular Ca2+ with compromised mitochondria and downregulated CAMKII isoforms, PKA, CREB and BDNF. Pretreatment with VRP showed significant enhancement in the architecture of the brain and in the behavioral tests as indicated by the measured parameters. Moreover, morning VRP exhibited better neuroprotective profile compared to the evening therapy. Conclusions VRP highlighted a multilevel of neuroprotection through anti-inflammatory activity, Ca2+ blockage, and regulation of Ca2+-dependent genes. Furthermore, chronotherapy of VRP administration should be consider to achieve best therapeutic efficacy. Graphical Abstract

To evaluate the potential role of vascular cell adhesion molecule-1 (VCAM-1), an endothelial factor, in endothelial dysfunction in rheumatoid arthritis (RA) patients, and to determine its relation to disease activity, oxidative stress, and inflammatory markers.Methods: This study was designed as a cross-sectional casecontrol study. One-hundred patients with RA were selected from out-

This study aimed to investigate the possible ameliorative effects of co-supplementation with Mg2+ and treadmill exercise on memory deficit in aged rats. Fifty male albino rats (10 young and 40 aged rats) were divided into 5 groups (10 rats/group): young, aged sedentary, aged exercised, aged Mg2+-supplemented, and aged exercised and Mg2+-supplemented. Memory was assessed using the Y-maze and novel object recognition tests. Plasma samples were collected for measurement of C-reactive protein (CRP). Subsequently, brain malondialdehyde and catalase levels were measured. Histological and immunohistochemical analyses of the hippocampi were performed. Our results showed impaired memory in aged sedentary rats, with significantly elevated plasma CRP and brain malondialdehyde levels and decreased brain catalase. The hippocampus of aged sedentary rats showed cellular degeneration, downregulation of synaptophysin (SYP) and proliferating cell nuclear antigen (PCNA), and upregulation of glial fibrillary acidic protein (GFAP) and caspase-3. Mg2+ supplementation and/or treadmill exercise significantly improved memory tests in aged rats, which could be explained by the upregulation of hippocampal SYP and PCNA expression and downregulation of GFAP and caspase-3 expression with antioxidant and anti-inflammatory mechanisms. The combined therapy had a better effect than both treatments alone, confirming the role of Mg2+ supplementation with physical exercise in enhancing age-related memory deficit. Novelty: Magnesium supplementation with treadmill exercise improves memory deficit in aged rats. The possible mechanisms are upregulation of the hippocampal synaptophysin and PCNA, downregulation of GFAP and caspase-3, the antioxidant and anti-inflammatory mechanisms.

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