الفهرس 
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Abstract
It has been well documented that curcumin possesses a variety of important pharmacological activities including anticancer, antimicrobial, anti-inflammatory anti-amyloid, antioxidant, and neuroprotective effects. Curcumin Nanoparticles have been suggested to have a potential therapeutic role in neurodegenerative diseases.
Multiple sclerosis is an auto-immune demyelinating disease that leaves the patients with disabilities. Conventional drug therapies for MS are not able to stop the degeneration of nerve tissue because current treatments focus on reducing the inflammatory lesions within the CNS but do not enhance endogenous myelin repair.
The present study was conducted to look at the patho histological changes of cuprizone induced demyelination on the white matter of mice brain, to explore the role of Curcumin Nanoparticles in repair of the toxic model of cuprizone, aiming to discover therapeutic strategies to replace myelin.
Cuprizone model of multiple sclerosis was introduced by feeding mice daily with cuprizone (bis-cyclohexanone oxaldihydrazone) mixed with standard chow starting with 0.03 g daily for the first 2 weeks to induce acute MS then reducing the dose to 0.02 g daily for the last 4 weeks inducing a sort of chronic MS.
The present study was carried out on 36 adult female black mice. They were randomly divided into four groups, 9 animals each:
• group I: (control group): Mice were fed with cuprizone-free diet.
• group II: Mice were fed with cuprizone-containing diet.
• group III: Represent the acute phase of motor and behavioural changes.
Mice were fed with the cuprizone-containing diet for 6 weeks, and were treated (two weeks following the start of cuprizone feeding) with curcumin nanoparticles purchased from One Planet Nutrition company in the USA, which is already prepared and ready to use in the form of powder. group IV: Represent the chronic phase of motor & behavioural changes.
Mice were fed with a cuprizone-containing diet for 6 weeks, and were treated (after four to five weeks following the start of cuprizone feeding) with curcumin nano particles.
Neurological and behavioural tests were conducted for all mice at end of the 4th week and 6th week (before the termination of the experiment) to check long-term memory and motor performance, using rotarod, open field, and passive avoidance tests
By the end of the experimental period, mice were sacrificed by decapitation. The brain was excised carefully, the corpus callosum was obtained for further histological, biochemical and immunohistochemical analysis:
- Histological studies using a light microscope: the specimens were fixed in 10% phosphate buffered formaldehyde (pH 7.4) for 24 h at room temperature for histological processing using two types of stains:
Haematoxylin and Eosin stain to assess for inflammatory infiltration, and Luxol fast blue (LFB) stain (special stain for myelin to assess the degree of demyelination/remyelination.
- Immunohistochemical staining for detection of CD4 and CD8 counts and ratios.
- Immunoflourescence imaging to visualize fluorescent Curcumin nano particles inside the tissues.
- Measurement of the oxidative stress; the SOD activity level and MDA level in the corpus callosum.
Histopathological study, in the demyelination group, revealed extensive demyelination of corpus callosum axons while in Curcumin nanoparticles, treated groups, remyelinated fibres appeared. Groups (III and IV), in the present study, had much lower inflammatory and demyelination scores (P<0.05). Additionally, group III had much lower inflammation scores and demyelination scores (P<0.05) as compared to group IV.
According to behaviour and neurological tests, cuprizone intake for six weeks precipitated motor deficit and impaired long-term memory. On the other hand, treatment with CurNPs improved both.
Cuprizone intoxication raised the MDA level in the corpus callosum and in turn decreased the SOD activity. In the CurNPs treated groups, the SOD activity raised up much more than the demyelination group.
The present study provided an evidence for the bioactive role of Cur NPs in the treatment of MS model in mice through its action as a potent immune modulator agent that prevents auto reactivity through its effect on the frequency and function of CD4+T, and CD8+Tcells. CurNPs decreased the count of CD8+Tcells which was elevated in Cuprizone group. In addition its role as potent antiflammatory was evidenced via decreasing the inflammatory scores in CurNPs treated groups, also its role as potent antioxidant increasing the level of SOD; which is the cornerstone in protection against ROS, leading to an increase in the antioxidant defense of the brain. Lastly and importantly, its precious effect of decreasing demyelination scores and demyelination patches in CurNPs treated groups.