http://www.nature.com/jcbfm/journal/v26/n4/full/9600212a.html
Abstract
We have previously shown that
neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if
administered before focal stroke. Here, we examined the therapeutic
window and functional recovery after NRG-1 treatment in rats subjected
to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of
reperfusion. Neuregulin-1 (2.5 ng/kg bolus, 1.25 ng/kg/min infusion)
reduced infarct volume by 89.2%
41.9% (means.d.; n=8; P less than 0.01)
if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%52.6%; n=7; P less than 0.01) and 12 h (57.0%20.8%; n=8; Pless than 0.01)
after reperfusion. Neuregulin-1 administration also resulted in a
significant improvement of functional neurologic outcome compared with
vehicle-treated animals (32.1%5.7%; n=9; Pless than 0.01).
The neuroprotective effect of the single administration of NRG-1 was
seen as long as 2 weeks after treatment. Neurons labeled with the
neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in
the cortex, but the numbers were significantly reduced after NRG-1
treatment. These results indicate that NRG-1 is a potent neuroprotective
compound with an extended therapeutic window that has practical
therapeutic potential in treating individuals after ischemic brain
injury.
41.9% (means.d.; n=8; P less than 0.01)
if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%52.6%; n=7; P less than 0.01) and 12 h (57.0%20.8%; n=8; Pless than 0.01)
after reperfusion. Neuregulin-1 administration also resulted in a
significant improvement of functional neurologic outcome compared with
vehicle-treated animals (32.1%5.7%; n=9; Pless than 0.01).
The neuroprotective effect of the single administration of NRG-1 was
seen as long as 2 weeks after treatment. Neurons labeled with the
neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in
the cortex, but the numbers were significantly reduced after NRG-1
treatment. These results indicate that NRG-1 is a potent neuroprotective
compound with an extended therapeutic window that has practical
therapeutic potential in treating individuals after ischemic brain
injury.
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