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1.
iScience ; 27(1): 108744, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38235338

ABSTRACT

In an innovative experiment, we detected ultraweak photon emission (UPE) from the hippocampus of male rat brains and found significant correlations between Alzheimer's disease (AD), memory decline, oxidative stress, and UPE intensity. These findings may open up novel methods for screening, detecting, diagnosing, and classifying neurodegenerative diseases, particularly AD. The study suggests that UPE from the brain's neural tissue can serve as a valuable indicator. It also proposes the development of a minimally invasive brain-computer interface (BCI) photonic chip for monitoring and diagnosing AD, offering high spatiotemporal resolution of brain activity. The study used a rodent model of sporadic AD, demonstrating that STZ-induced sAD resulted in increased hippocampal UPE, which was associated with oxidative stress. Treatment with donepezil reduced UPE and improved oxidative stress. These findings support the potential utility of UPE as a screening and diagnostic tool for AD and other neurodegenerative diseases.

2.
Spinal Cord ; 62(1): 17-25, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38001173

ABSTRACT

STUDY DESIGN: Preclinical pharmacology. OBJECTIVES: Our study aims to evaluate the combined effect of Methylprednisolone (MP) and growth factor-rich serum (GFRS) on structural and functional recovery in rats following spinal cord injury (SCI). SETTING: Shiraz University of Medical Sciences, Shiraz, Iran METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: sham group (laminectomy); SCI group (the spinal cord clip compression model); SCI-MP group (30 mg/kg MP was administrated intraperitoneally (IP) immediately after SCI); SCI-GFRS group (GFRS (200 µl, IP) was administrated for six consecutive days); and SCI-MP + GFRS group (the rats received MP (30 mg/kg, IP) immediately after SCI, and GFRS (200 µl, IP) for six consecutive days). Motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) scale. After 4 weeks, we conducted the rotarod test, then removed and prepared the spinal cords (including the epicenter of injury) for stereological and histological estimation, and biochemical assays. RESULTS: The results showed that MP and GFRS combining treatment enhanced functional recovery, which was associated with a decrement in lesion volume, increased spared white and gray matter volume, reduced neuronal loss, as well as decreased necrosis and hemorrhage after SCI. Moreover, administration of MP and GFRS inhibited lipid peroxidation (malondialdehyde (MDA) content), and increased antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) after rat SCI. CONCLUSIONS: We suggests that the combination treatment of MP and GFRS may ameliorate the structure and functional changes following SCI by reducing oxidative stress, and increasing the level of antioxidants enzymes.


Subject(s)
Neuroprotective Agents , Spinal Cord Compression , Spinal Cord Injuries , Rats , Male , Animals , Methylprednisolone/therapeutic use , Rats, Sprague-Dawley , Neuroprotective Agents/pharmacology , Spinal Cord/pathology , Intercellular Signaling Peptides and Proteins/pharmacology , Intercellular Signaling Peptides and Proteins/therapeutic use
3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 4833-4849, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38157024

ABSTRACT

Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus.


Subject(s)
Administration, Intranasal , Behavior, Animal , Hippocampus , Insulin , Nitrosative Stress , Oxidative Stress , Rats, Wistar , Streptozocin , Animals , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Male , Streptozocin/toxicity , Oxidative Stress/drug effects , Nitrosative Stress/drug effects , Behavior, Animal/drug effects , Rats , Disease Models, Animal , Maze Learning/drug effects , Injections, Intraventricular , Memory/drug effects
4.
Stem Cells Int ; 2023: 7852394, 2023.
Article in English | MEDLINE | ID: mdl-37081849

ABSTRACT

According to strong evidence, diabetes mellitus increases the risk of cognitive impairment. Mesenchymal stem cells have been shown to be potential therapeutic agents for neurological disorders. In the current study, we aimed to examine the effects of Wharton's jelly-derived mesenchymal stem cell-conditioned medium (WJMSC-CM) on learning and memory, oxidative stress, apoptosis, and histological changes in the hippocampus of diabetic rats. Randomly, 35 male Sprague Dawley rats weighing 260-300 g were allocated into five groups: control, diabetes, and three diabetic groups treated with insulin, WJMSC-CM, and DMEM. The injections of insulin (3 U/day, S.C.) and WJMSC-CM (10 mg/week, I.P.) were done for 60 days. The Morris water maze and open field were used to measure cognition and anxiety-like behaviors. Colorimetric assays were used to determine hippocampus glutathione (GSH), malondialdehyde (MDA) levels, and antioxidant enzyme activity. The histopathological evaluation of the hippocampus was performed by Nissl staining. The expression levels of Bax, Bcl-2, BDNF, and TNF-α were detected by real-time polymerase chain reaction (RT-PCR). According to our findings, WJMSC-CM significantly reduced and increased blood glucose and insulin levels, respectively. Enhanced cognition and improved anxiety-like behavior were also found in WJMSC-CM-treated diabetic rats. In addition, WJMSC-CM treatment reduced oxidative stress by lowering MDA and elevating GSH and antioxidant enzyme activity. Reduced TNF-α and enhanced Bcl-2 gene expression levels and elevated neuronal and nonneuronal (astrocytes and oligodendrocytes) cells were detected in the hippocampus of WJMSC-CM-treated diabetic rats. In conclusion, WJMSC-CM alleviated diabetes-related cognitive impairment by reducing oxidative stress, neuroinflammation, and apoptosis in diabetic rats.

5.
World Neurosurg ; 167: e317-e322, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35963607

ABSTRACT

BACKGROUND: One of the major problems in neurosurgical procedures is fibrosis formation. Therefore, the prevention of fibrosis is an important issue in spinal cord injury that needs to be addressed. No approved therapy has yet been found, and epidural fibrosis (EF) is a huge treatment challenge. In this regard, new drugs that can effectively prevent EF are still being considered. Hence, this study aimed to investigate the effects of dexamethasone (DEX), nanocurcumin (Nano-CUR), and coenzyme Q10 (CoQ10) on the prevention of EF in a rat laminectomy model. METHODS: Thirty-five Sprague-Dawley male rats were randomly divided into 5 groups: sham group, laminectomy group, laminectomy + DEX group, in which 0.5 ml DEX (8 mg/ml) was applied locally on the laminectomy area, laminectomy + Nano-CUR group, in which 100 mg/kg Nano-CUR was administered intraperitoneally once a day for 7 days, and laminectomy + CoQ10 group, in which 30 mg/kg CoQ10 was administered once daily intraperitoneally for 7 days. After 4 weeks, the vertebral columns were removed from L1 and L3 and prepared for histopathological assays. RESULTS: The local administration of DEX could not improve the histological parameters, and EF was induced by laminectomy after 4 weeks. On the other hand, Nano-CUR could ameliorate EF at the laminectomy site compared to the laminectomy group, but the difference was not statistically significant. CoQ10 significantly reduced EF (P < 0.05), collagen density (P < 0.01), and inflammation in the arachnoid layer (P < 0.01). CONCLUSIONS: Our findings showed that Nano-CUR and CoQ10 had the potential to be used for treatment of EF.


Subject(s)
Epidural Space , Laminectomy , Rats , Male , Animals , Rats, Sprague-Dawley , Laminectomy/adverse effects , Epidural Space/pathology , Fibrosis , Dexamethasone/pharmacology , Dexamethasone/therapeutic use
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