title: Neuroprotective effects of pretreatment with minocycline on memory impairment following cerebral ischemia in rats.
abstract: Cerebral ischemia leads to memory impairment that is associated with loss of hippocampal CA1 pyramidal neurons. Neuroinflammation and oxidative stress may be implicated in the pathogenesis of ischemia/reperfusion damage. Minocycline has anti-inflammatory and antioxidant properties. We investigated the neuroprotective effects of minocycline in rats subjected to cerebral ischemia/reperfusion injury. Thirty male rats were divided into three groups: control, sham, and minocycline-pretreated group. Minocycline (40 mg/kg) was injected intraperitoneally immediately before surgery, and then ischemia was induced by occlusion of common carotid arteries for 20 min. Seven days after reperfusion, the Morris water-maze task was used to evaluate memory. Nissl staining was also performed to analyze pyramidal cell damage. We measured the contents of malondialdehyde and proinflammatory cytokines in the hippocampus by the thiobarbituric acid method and enzyme-linked immunosorbent assay, respectively. Microglial activation was also investigated by Iba1 immunostaining. The results showed that pretreatment with minocycline prevented memory impairment induced by cerebral ischemia/reperfusion. Minocycline pretreatment also significantly attenuated ischemia-induced pyramidal cell death and microglial activation in the CA1 region and reduced the levels of malondialdehyde and proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of ischemic rats. Minocycline showed neuroprotective effects on cerebral ischemia-induced memory deficit probably through its anti-inflammatory and antioxidant activities.
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Naderi
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sabetkasaei
authors.forename: Siavash
authors.initials: S
authors.lastname: Parvardeh
authors.forename: Taraneh
authors.initials: T
authors.lastname: Moini Zanjani
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D008911:Minocycline