Previous results from our laboratory have shown that blockade of the
substance P (SP) pathway with an NK1
tachykinin receptor antagonist significantly reduces blood brain barrier breakdown,
cerebral edema and functional deficits following
ischemic stroke. However, it is unclear whether removal of all
neuropeptides is more efficacious than blocking SP alone. As such, the aim of the present study was to determine the effect of
neuropeptide depletion with
capsaicin pre-treatment on functional outcome following
acute ischemic stroke in rats. Animals received 125 mg/kg of
capsaicin or equal volume of saline vehicle, administered subcutaneously over a 3-day period. At 14 days following treatment animals were subject to 2h of
middle cerebral artery occlusion followed by reperfusion. A subset of animals was treated with an NK1
tachykinin receptor antagonist (
NAT) or vehicle at 4h after the onset of
stroke only. The functional outcome of animals was assessed for a 7-day period following
stroke using a rotarod device, the bilateral asymmetry test, modified neurological severity score, open field and angleboard. Although
capsaicin pre-treatment improved outcome, treatment with an NK1
tachykinin receptor antagonist was superior in improving post-
stroke functional outcome. This data suggests that some
neuropeptides may play a beneficial role following
stroke, whilst others such as SP are deleterious.