title: Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.
abstract: Oxidative stress is a significant contributor to the secondary sequelae of traumatic brain injury (TBI), and may mediate subsequent neurobehavioral deficits and histopathology. The present study examined the neuroprotective effects of bromocriptine (BRO), a dopamine D2 receptor agonist with significant antioxidant properties, on cognition, histopathology, and lipid peroxidation in a rodent model of focal brain trauma. BRO (5 mg/kg) or a comparable volume of vehicle (VEH) was administered intraperitoneally 15 min prior to cortical impact or sham injury. In experiment 1, spatial learning was assessed in an established water maze task on post-surgery days 14-18, followed by quantification of hippocampal cell survival and cortical lesion volume at 4 weeks. In experiment 2, rats were sacrificed 1 hr post-surgery, and malondialdehyde (MDA), the end product of lipid peroxidation, was measured in the frontal cortex, striatum, and substantia nigra using a thiobarbituric acid reactive substances assay. The TBI+BRO group was significantly more adept at locating a hidden platform in the water maze compared to the TBI+VEH group and also exhibited a greater percentage of surviving CA3 hippocampal neurons. TBI increased MDA in all examined regions of the VEH-treated, but not BRO-treated group versus SHAMs. MDA was significantly decreased in both the striatum (4.22 +/- 0.52 versus 5.60 +/- 0.44 nmol per mg/tissue +/- SEM) and substantia nigra (4.18 +/- 0.35 versus 7.76 +/- 2.05) of the TBI+BRO versus TBI+VEH groups, respectively, while only a trend toward decreased MDA was observed in the frontal cortex (5.44 +/- 0.44 versus 6.96 +/- 0.77). These findings suggest that TBI-induced oxidative stress is attenuated by acute BRO treatment, which may, in part, explain the benefit in cognitive and histological outcome.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. klineae@upmc.edu
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Kline
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Massucci
authors.forename: Xiecheng
authors.initials: X
authors.lastname: Ma
authors.forename: Ross D
authors.initials: RD
authors.lastname: Zafonte
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D001971:Bromocriptine / Q000494:pharmacology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017392:Thiobarbituric Acid Reactive Substances; D001971:Bromocriptine