title: Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy.
abstract: Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Dawley rats (n = 10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.
authors.affiliation: Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Republic of China.
authors.forename: W T
authors.initials: WT
authors.lastname: Lee
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Shen
authors.forename: C
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D014227:Triazines; D001224:Aspartic Acid; D016291:Dizocilpine Maleate; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; C015392:3-nitropropionic acid; D000077213:Lamotrigine