title: Delayed treatment with nicotinamide inhibits brain energy depletion, improves cerebral microperfusion, reduces brain infarct volume, but does not alter neurobehavioral outcome following permanent focal cerebral ischemia in Sprague Dawley rats.
abstract: Delayed treatment with nicotinamide (NAm) reduces infarction induced by middle cerebral artery occlusion (MCAO) in rats. This study explored some potential mechanisms by which delayed NAm treatment may confer protection in the brain of Sprague-Dawley rats following permanent MCAO (pMCAO). NAm (500 mg/kg) or vehicle was given 2 h after the onset of pMCAO. Cortical microperfusion, brain and rectal temperature were serially measured. Neurobehavioral examinations were performed at 24 h post-ischemia followed by sacrifice for histologic assessment. Some rats were also sacrificed at 4 h post-ischemia for analyses of ATP, ADP, AMP, and adenosine. Permanent MCAO induced spontaneous hyperthermia and a sharp decrease in cortical microperfusion, ATP concentration, and the sum of adenine nucleotides (p < 0.05). At 4 h post-ischemia, NAm improved ATP recovery, the sum of adenine nucleotides (p < 0.05) and attenuated the ischemia-induced systemic hyperthermia (p < 0.05) without affecting brain temperature or cortical microperfusion. At 24 h, NAm improved cortical microperfusion in the ischemic hemisphere and reduced total infarct volume (p < 0.05), but did not affect behavioral scores. The data suggest that NAm attenuated brain damage following pMCAo initially by improving cerebral bioenergetic metabolism during the sub-acute phase of ischemia, followed by a delayed improvement in microvascular perfusion.
authors.affiliation: Institute of Biomedical Engineering, National Cheng Kung Univeristy, Taiwan.
authors.forename: E-Jian
authors.initials: EJ
authors.lastname: Lee
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
authors.forename: Guan-Liang
authors.initials: GL
authors.lastname: Chang
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Li
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Chen
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lee
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Maynard
mesh_terms: D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005334:Fever / Q000209:etiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009536:Niacinamide / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D009536:Niacinamide; D000255:Adenosine Triphosphate; D000225:Adenine