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Gh Popescu B.F.,University of Saskatchewan | Gh Popescu B.F.,Cameco Neuroscience Research Center | Lucchinetti C.F.,Mayo Medical School
BMC Neurology | Year: 2012

Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS. © 2012 Gh Popescu and Lucchinetti; licensee BioMed Central Ltd.

Adiele L.C.,Madonna University of Nigeria | Adiele L.C.,Federal University of Technology Owerri | Adiele R.C.,University of Saskatchewan | Adiele R.C.,Cameco Neuroscience Research Center | Enye J.C.,Madonna University of Nigeria
Asian Pacific Journal of Tropical Medicine | Year: 2014

Objective: To investigate the wound healing property of Napoleona vogelii leaf extract in folkloric medicine. Methods: Both sexes of adult albino rats (n=25) were used in this study and another group (n=30) were subjected to acute toxicity test (LD50) of the plant extract. For the LD50, three randomized groups of 5 rats were first treated with 10, 100, 1 000 mg/kg body weight (bw), orally. This was followed by a second treatment of 1500, 3000, and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality. Incision wounds (1.5 cm) were created on the skin of five groups of 5 rats using surgical blade under anesthesia. The first group was topically treated with petroleum jelly alone, group 2 was topically applied 400 mg/mL w/v of the reference drug, Neobacin, while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract, respectively. Results: The percentage yield of the extract was 49.80% w/w dry matter. The phytochemical analysis revealed several bioactive constituents including glycosides, tannins, alkaloids, perpenoids, saponins, steroids, proteins, and carbohydrates. The LD50 was beyond our experimental limit and was not determined. Increased concentrations (5, 20, and 50 mg/mL w/v) of the extract had significant (ANOVA, P<0.05) healing effect on the incision wounds giving rise to 125%-140% while treatment with Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control (100%). Conclusions: These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity, substantiating its use as a wound healer in folkloric medicine. © 2014 Hainan Medical College.

Adiele R.C.,University of Saskatchewan | Adiele R.C.,Cameco Neuroscience Research Center | Fakae B.B.,University of Nigeria | Fakae B.B.,University of Port Harcourt | Isuzu I.U.,University of Nigeria
Asian Pacific Journal of Tropical Medicine | Year: 2013

Objective: To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata (S. longepedunculata) root extract as an anthelmintic in folkloric medicine. Methods: Albino mice were infected with infective third (L3) larval stage of Heligmosomoides polygyrus (H. polygyrus) by esophageal intubation. Following establishment of the adult worms in the intestine, the mice were treated with 0-2 000 mg/kg body weight (bw) of methanolic root extract of S. longepedunculata and 100 mg/kg bw of pyrantel embonate, the reference drug in vivo. Bioactivity and larvicidal effects of the extract were tested by exposing brine shrimps (Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of Heligmosomoides contortus (H. contortus) and H. polygyrus to 0.00-2.50 mg/mL of the extract in vitro. Results: The percentage yield of the extract was 7.13% w/w dry matter. The brine shrimps toxicity bioassay resulted in an LC50 of 74.18 μg/mL. The extract had a significant, dose-dependent larvicidal effect on the L3 stage of H. contortus and H. polygyrus with the terminal effect of 75% and 70% at the highest exposure concentrations, respectively. The extract however, did not affect the number of worm eggs per gram (epg) of fecal materials (P<0.05) and total worm burden (twb) of adult H. polygyrus in infected mice. Treatment with pyrantel embonate significant reduced both the fecal egg count and twb to 0 compared to the untreated control (P<0.05). Conclusions: These results indicate that S. longepedunculata root extract contains potent bioactive compounds and has larvicidal effect on L3 stage of H. contortus and H. polygyrus, substantiating its use as anthelmintic in alternative medicine. © 2013 Hainan Medical College.

Ji S.,University of Saskatchewan | Doucette J.R.,University of Saskatchewan | Doucette J.R.,Cameco Neuroscience Research Center | Nazarali A.J.,University of Saskatchewan | Nazarali A.J.,Cameco Neuroscience Research Center
Journal of Molecular Cell Biology | Year: 2011

Although Sirt2 is primarily expressed in oligodendrocytes of the central nervous system, its role in oligodendroglial lineage differentiation is not fully understood. Our findings demonstrate that the transcription factor Nkx2.2 binds to the Sirt2 promoter via histone deacetylase 1 (HDAC-1), the binding site for Nkx2.2 maps close to the start codon of the Sirt2 gene, and Nkx2.2 negatively regulates Sirt2 expression in CG4 cells, an oligodendroglial precursor cell line. HDAC-1 knock-down not only significantly attenuates the binding capacity of Nkx2.2 to the Sirt2 promoter but also releases repression of Sirt2 expression by Nkx2.2. Nkx2.2 over-expression down-regulates Sirt2 expression and delays differentiation of CG4 cells; in contrast, up-regulation of Sirt2 does not impact Nkx2.2 expression level. Sirt2 knock-down via RNAi or inhibition of Sirt2 by sirtinol, a Sirt2 activity inhibitor, blocks CG4 cell differentiation. Over-expression of Sirt2 facilitates CG4 cell differentiation at both molecular and cellular levels, enhancing expression of myelin basic protein and facilitating the growth of cell processes. We have conclusively demonstrated that Sirt2 enhances CG4 oligodendroglial differentiation and report a novel mechanism through which Nkx2.2 represses CG4 oligodendroglial differentiation via Sirt2. © The Author 2011.

Doucette J.R.,University of Saskatchewan | Doucette J.R.,Cameco Neuroscience Research Center | Jiao R.,University of Saskatchewan | Nazarali A.J.,Cameco Neuroscience Research Center | Nazarali A.J.,University of Saskatchewan
Cellular and Molecular Neurobiology | Year: 2010

During aging, there is a decrease both in the stability of central nervous system (CNS) myelin once formed and in the efficiency of its repair by oligodendrocytes (OLs). To study CNS remyelination during aging, we used the cuprizone (a copper chelator) mouse model. Inclusion of cuprizone in the diet kills mature OLs and demyelinates axons in the rostral corpus callosum (CC) of mice, which enabled us to characterize age-related changes (i.e., 2-16 months of age) in glial cell response during the recruitment (i.e., demyelination) and differentiation (i.e., remyelination) phases of myelin repair. We have found that the time between 12 and 16 months of age is a critical period during which there is an age-related decrease in the number of OL lineage cells (Olig2 Nuc+ve/GFAP-ve cells) in the rostral CC of both control mice and mice recovering from cuprizone-induced demyelination. Our results also show there was an age-related impaired recruitment of progenitor cells to replace lost OLs in spite of there being no major age-related decrease in the size of the progenitor cell pool (PDGFαR+ve/GFAP-ve, and Olig2Nuc+ve/ PDGFαR+ve cells). However, there were cuprizoneinduced increased numbers of astrocyte progenitor cells (Olig2Cyto+ve/PDGFαR+ve) in these same mice; thus PDGFαR+ve progenitor cells in mice as old as 16 months of age retain the ability to differentiate into astrocytes, with this fate choice occurring following cytoplasmic translocation of Olig2. These data reveal for the first time agerelated differences in the differentiation of PDGFαR+ve progenitor cells into OLs and astrocytes and lead us to suggest that during aging there must be a transcriptional switch mechanism in the progenitor cell fate choice in favor of astrocytes. This may at least partially explain the age-related decrease in efficiency of OL myelination and remyelination. © Springer Science+Business Media, LLC 2010.

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