- •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.
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.
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- Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.Stroke. 1993; 24: 35-41
- Interventional stroke therapy: the potential benefit of direct intra-arterial infusion.Rev. Cardiovasc. Med. 2002; 3: S92-S99
- Endovascular treatment strategies for acute ischemic stroke.Int. J. Stroke. 2011; 6: 511-522
- ARIA, a protein that stimulates acetylcholine-receptor synthesis, is a member of the neu ligand family.Cell. 1993; 72: 801-815
- Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century.Lancet Neurol. 2003; 2: 43-53
- Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture.Stroke. 2003; 34: 214-223
- Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen-glucose deprivation in-vitro.Neuroscience. 1995; 68: 615-619
- Intravenous thrombolysis with recombinant tissue-plasminogen activator for acute hemispheric stroke — the European Cooperative Acute Stroke Study (ECASS).JAMA. 1995; 274: 1017-1025
- Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.Lancet. 2004; 363: 768-774
- Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.Stroke. 2003; 34: e109-e137
- Glial growth factor 2 promotes functional recovery with treatment initiated up to 7 days after permanent focal ischemic stroke.Neuropharmacology. 2010; 59: 640-649
- Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia.Brain Res. 2007; 1184: 277-283
- Neuregulin-1 inhibits neuroinflammatory responses in a rat model of organophosphate-nerve agent-induced delayed neuronal injury.J. Neuroinflammation. 2015; 12: 64
- Ischemic cell death in brain neurons.Physiol. Rev. 1999; 79: 1431-1568
- Effect of neuregulin-1 on histopathological and functional outcome after controlled cortical impact in mice.J. Neurotrauma. 2007; 24: 1817-1822
- Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke.Ann. Neurol. 1997; 41: 574-580
- Secondary deterioration of apparent diffusion coefficient after 1-hour transient focal cerebral ischemia in rats.J. Cereb. Blood Flow Metab. 2000; 20: 1474-1482
- Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.Stroke. 2015; 46: 419-424
- Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke.Neurology. 1997; 49: 113-119
- Neuregulin-1 attenuates mortality associated with experimental cerebral malaria.J. Neuroinflammation. 2014; 11: 9
- Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead.Stroke. 2011; 42: 2351-2355
- Interobserver agreement for the assessment of handicap in stroke patients.Stroke. 1988; 19: 604-607
- Absolute measurements of water content using magnetic resonance imaging: preliminary findings in an in vivo focal ischemic rat model.Magn. Reson. Med. 2000; 43: 146-150
- Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue-plasminogen activator.Am. J. Neuroradiol. 1993; 14: 3-13
- Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke.Biochem. Biophys. Res. Commun. 2004; 322: 440-446
- Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression.Neurobiol. Dis. 2005; 19: 461-470
- Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke.J. Cereb. Blood Flow Metab. 2006; 26: 527-535
- A fast multiparameter MRI approach for acute stroke assessment on a 3 T clinical scanner: preliminary results in a non-human primate model with transient ischemic occlusion.Quant. Imaging Med. Surg. 2014; 4: 112-122
- Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study.PLoS ONE. 2015; 10: e0117290
Published online: June 26, 2015
Accepted: June 25, 2015
Received in revised form: May 25, 2015
Received: March 9, 2015
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.