The Past and Future of Neuroprotection in Cerebral Ischaemic Stroke

Abstract

Following the realization that cerebral tissue may survive for hours after an ischaemic insult, several agents with neuroprotective properties in small-animal models of cerebral ischaemia have been tested in patients with acute ischaemic stroke (AIS). Initial attempts at translating the positive effects of these agents from animal models to patients were unsuccessful, possibly as a result of poorly planned experiments in models of ischaemia, and/or clinical trials of AIS that were not optimized to show a positive effect. Newer neuroprotective agents that are believed to act later in the ischaemic cascade may offer a greater chance of success. However, before these agents can be introduced into clinical practice they must undergo assessment in rodent and large-animal models of AIS and, in particular, the dose-response relationship and the treatment time window should be defined. This should be followed by evaluation in carefully designed clinical trials of adequate power, involving subjects receiving an appropriate dose within an optimum time window following the onset of symptoms. There is hope that such careful strategies may guide continued progress in neuroprotective drug development.

Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

“…No neuroprotective agents exist to protect against an ischemic cerebrovascular injury [29] . PF was isolated from one herbal medicine that has been demonstrated to be neuroprotective in the MCAO rat model of ischemic stroke, although the underlying mechanism is unknown.…”

The Continued Promise of Neuroprotection for Acute Stroke Treatment

“…(Rother, 2008) This again demonstrated the urgent need for a reconsideration of our strategies for neuroprotection for acute ischemic stroke treatment. As pointed out by other investigators (Donnan and Davis, 2008;Hussain and Shuaib, 2008;Shuaib and Hussain, 2008), research on neuroprotection is still possible and we should continue in searching for an effective neuroprotectant. But where are the correct directions and what could be a better concept for neuroprotection?…”

The Continued Promise of Neuroprotection for Acute Stroke Treatment

“…(Rother, 2008) This again demonstrated the urgent need for a reconsideration of our strategies for neuroprotection for acute ischemic stroke treatment. As pointed out by other investigators (Donnan and Davis, 2008;Hussain and Shuaib, 2008;Shuaib and Hussain, 2008), research on neuroprotection is still possible and we should continue in searching for an effective neuroprotectant. But where are the correct directions and what could be a better concept for -3 -neuroprotection?…”