title: Spatio-temporal assessment of the neuroprotective effects of neuregulin-1 on ischemic stroke lesions using MRI.
abstract: The neuroprotective effects of neuregulin-1 (NRG-1) on stroke lesions were assessed longitudinally in rats with middle cerebral artery occlusion (MCAo) using MRI. Sprague-Dawley rats (n=16, 250±20g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20min post-occlusion. A single 50μl bolus dose of NRG-1 or vehicle was administered into the left internal carotid artery immediately prior to MCAo. The expansion of the ischemic lesion into the cortex was attenuated by NRG-1 over a 48-hour (h) time span as measured by diffusion weighted imaging (DWI). The final infarct volumes of NRG-1 treated rats were significantly smaller than those of the vehicle treated rats at 48h (264.8±192.1 vs. 533.4±175.5mm(3), p<0.05). The NRG-1 treated rats were further subdivided into 2 subgroups according to their CBF reduction during stroke surgery: mild ischemia (<70% CBF reduction) or severe ischemia (>70% CBF reduction). In particular, ischemic infarction was not usually observed in the cortex of NRG-1 treated rats with mild ischemia at 3 and 48h post-occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48h post-ischemia. In summary, the neuroprotective effect of NRG-1 in the pMCAo stroke model was demonstrated by prevention of ischemic lesion expansion, reduced infarct volume and protection of neurons from ischemic damage.
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
authors.forename: Silun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Paudyal
authors.affiliation: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA. Electronic address: bford@msm.edu.
authors.forename: Byron D
authors.initials: BD
authors.lastname: Ford
authors.affiliation: Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Electronic address: xzhang8@emory.edu.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D008279:Magnetic Resonance Imaging; D020890:Neuregulin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D059906:Neuroimaging; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D062211:Spatio-Temporal Analysis; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D020890:Neuregulin-1; D018696:Neuroprotective Agents
keywords: Ischemia; MCAo; MRI; NRG-1; Rat; Stroke