Effects of Intranasal Nerve Growth Factor for Acute Ischemic Stroke

Overview

Stroke remains one of the leading causes of death and adult disability worldwide. Yet, currently, the only accepted treatment for acute ischemic stroke(AIS) is recanalization of occluded arteries. Thrombolysis with tissue plasminogen activator, limited by its narrow therapeutic time window and the concern of hemorrhagic complication, is still uncommon in use. The other approach is to try to impede the ischemic cascade by targeting various components of the cascade that are deemed to be of importance, namely, a neuroprotection strategy. Nerve growth factor (NGF) plays extensive roles in preventing ischemic injury. Besides that, it is also involved in neurogenesis of the central nervous system (CNS). In addition, the levels of NGF protein and messenger RNA significantly decreased in the CNS at the first few hours and returned to normal levels several days later after middle cerebral artery occlusion (MCAO) in animal models. These observed results suggested that NGF was demanded in ischemic brain injury, but endogenous NGF is insufficient for the requirement and delivering exogenous ones will be blocked in entering into the CNS by the blood-brain barrier (BBB). Intracerebroventricular or intracerebral injection of NGF or grafting of NGF-producing cells may be less practicable due to invasiveness and safety concerns. Intranasal (IN) administration is a noninvasive and acceptable delivery strategy for drugs bypassing BBB and can deliver NGF to the CNS, which has been proved to show neuroprotective effects on brain injury. The effects of intranasal NGF in human ischemic stroke is still controversial that need further evaluation.

The proposed study is a randomized, double-blind, placebo-controlled trail of NGF, starting between 24 to 72 hours post acute ischemic stroke, continuing for 2 weeks.