title: Minocycline attenuates hypoxia-ischemia-induced neurological dysfunction and brain injury in the juvenile rat.
abstract: To investigate whether minocycline provides long-lasting protection against neonatal hypoxia-ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague-Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic-ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic-ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia-ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia-ischemia-induced brain injury and the associated neurological dysfunction.
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, 39216, USA.
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Shuying
authors.initials: S
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Pang
authors.forename: Philip G
authors.initials: PG
authors.lastname: Rhodes
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D020520:Brain Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007231:Infant, Newborn; D007274:Injections, Intraperitoneal; D007969:Leukomalacia, Periventricular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline