Spatio-temporal assessment of the neuroprotective effects of neuregulin-1 on ischemic stroke lesions using MRI

• Type of Material: Article
• Authors: Silun Wang, Emory University; Yonggang Li, Morehouse School of Medicine; Ramesh Paudyal, Emory University; Byron D. Ford, Morehouse School of Medicine; Xiaodong Zhang, Emory University
• Language: English
• Date: 2015-03-09
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier B.V. All rights reserved. CC BY NC ND 4.0
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jns.2015.06.055
• Title of Journal or Parent Work: Journal of the Neurological Sciences
• ISSN: 0022-510X
• Volume: 357
• Issue: 1-2
• Start Page: 28
• End Page: 34
• Grant/Funding Information: This project was supported in part by NCRR; and currently by the Office of Research Infrastructure Programs of NIH (OD P51OD011132, P51RR000165).
• Keywords: Spatio-Temporal Analysis; Laser-Doppler Flowmetry; Rat; Neuroprotective Agents; Cerebral Cortex; Stroke; Neuregulin-1; Ischemia; MCAo; Disease Models, Animal; Brain Ischemia; Rats; Neuroimaging; MRI; Infarction, Middle Cerebral Artery; Animals; NRG-1; Magnetic Resonance Imaging
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience

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 ± 20 g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20 min post-occlusion. A single 50 μl 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 48 h (264.8 ± 192.1 vs. 533.4 ± 175.5 mm3, 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 48 h post-occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48 h 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.