title: Adenosine A1 receptor agonist, N6-cyclohexyladenosine, protects myelin and induces remyelination in an experimental model of rat optic chiasm demyelination; electrophysiological and histopathological studies.
abstract: Chronic demyelinated lesions and subsequent functional impairment are resulted from eventual failure of remyelination process as seen in multiple sclerosis. Activation of adenosine A1 receptor is reported to be effective on neural stem cells (NSCs) proliferation and oligodendrocytes differentiation. Therefore, this study attempted to investigate the effect of A1 receptor agonist N6-cyclohexyladenosine (CHA), on lysolecithin (LPC) induced demyelination and remyelination in rat optic chiasm. The experiments were carried out on male Wistar rats using visual evoked potential recording, myelin staining by Luxol fast blue and histological evaluation of demyelinated and remyelinated axons within the area of lesion. CHA was administrated i.c.v. during demyelination or remyelination phases. As revealed by myelin staining, the most extent of demyelination occurred at 7th day post-lesion (dpl 7), but gradually myelination was restored toward control during days 14-28. VEP P1-latency and P1-N1 amplitude showed widespread demyelination on dpl 7 and 14 which consequently was reversed during days 14-28 post lesion. I.c.v. treatment of animals with CHA during demyelination phase (days 0-13) reduced the extent of demyelination. During remyelination phase (days 14-28), CHA was able to increase remyelination in both electrophysiological and histopathological studies. The effects of CHA seem to be due to its protective effect on myelinating cells and its regenerative effect through potentiating endogenous neural progenitors.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Asghari
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Azarnia
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009897:Optic Chiasm / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058907:Adenosine A1 Receptor Agonists; D018696:Neuroprotective Agents; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine