Highlights
- •NRG-1 shows significant neuroprotective effects in ischemic brains.
- •NRG-1 treated rats have smaller infarct volume and better neurological recovery.
- •NRG-1 treatment effect was influenced by CBF reduction during stroke.
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.
Keywords
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Article info
Publication history
Published online: June 26, 2015
Accepted:
June 25,
2015
Received in revised form:
May 25,
2015
Received:
March 9,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
