What will it take and who needs to be talked to to find out if this should be put into a clinical human trial? Or do we need to be our own guinea pigs because no one in the stroke medical world is willing to work on possibilities that may help survivors?
http://link.springer.com/article/10.1007/s12035-014-8830-6
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Abstract
We have previously
reported that angiotensin type 1 receptor (AT1R) blockade with
candesartan exerts neurovascular protection after experimental cerebral
ischemia. Here, we tested the hypothesis that a low, subhypotensive dose
of candesartan enhances neuroplasticity and subsequent functional
recovery through enhanced neurotrophic factor expression in rats
subjected to ischemia reperfusion injury. Male Wistar rats (290–300 g)
underwent 90 min of middle cerebral artery occlusion (MCAO) and received
candesartan (0.3 mg/kg) or saline at reperfusion and then once every
24 h for 7 days. Functional deficits were assessed in a blinded manner
at 1, 3, 7, and 14 days after MCAO. Animals were sacrificed 14-day
post-stroke and the brains perfused for infarct size by cresyl violet.
Western blot and immunohistochemistry were used to assess the expression
of growth factors and synaptic proteins. Candesartan-treated animals
showed a significant reduction in the infarct size [
t (13) = −5.5,
P = 0.0001] accompanied by functional recovery in Bederson [
F (1, 13) = 7.9,
P = 0.015], beam walk [
F (1, 13) = 6.7,
P = 0.023], grip strength [
F (1, 13) = 15.2,
P = 0.0031], and rotarod performance [
F (1, 14) = 29.8,
P
< 0.0001]. In addition, candesartan-treated animals showed
significantly higher expression of active metalloproteinase-3 (MMP-3),
laminin, and angiopoietin-1 (Ang-1). The expression of vascular
endothelial growth factor (VEGF) and brain-derived neurotrophic factor
(BDNF) and its receptor was significantly increased in the animals
treated with candesartan. Also, we observed significant increases in
neuroplasticity markers, synaptophysin, and PSD-95. These results
indicate that low-dose candesartan had a large and enduring effect on
measures of plasticity, and this accompanied the functional recovery
after ischemic stroke
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