Natural product based novel small molecules with promising neurotrophic, neurogenic and anti-neuroinflammatory actions can be developed as stroke therapeutics.

Abstract

Stroke is the world's second leading cause of death and a major cause of adult disability. Among the different kinds of stroke, ischemic stroke is the most widely prevalent type, causing high morbidity and mortality worldwide (Moskowitz et al., 2010). It is an intricate neurological disorder, characterized by reduced blood flow to the brain, deprivation of nutrients and oxygen and hence fails to maintain sustained ATP levels required to meet brain metabolic demands. This triggers diverse adaptive or maladaptive molecular and biochemical pathways and leads to changes in neural and glial functions. The therapeutic use of recombinant tissue plasminogen activator (rt-PA) at early time points of cerebral ischemic stroke, facilitates reperfusion and mitigates the loss of neuronal cells by intrinsic neural plasticity (Mehta et al., 2007). However, the delay of treatment makes it ineffective causing irreversible loss of cells in neural circuitry affecting the functional integrity due to infarct, eventually leading to neuromotor impairment, post-stroke depression, cognitive impairment, etc. Stroke deprives the brain nourishment, triggers diverse biochemical changes like reactive oxygen species (ROS) production, inflammation, calcium influx, glutamate excitotoxicity, etc, in the neuro-glial milieu of the brain. Drugs developed against these molecular targets proved effective in impeding the stroke damage, when given in combination with reperfusion agents. However, these therapeutics are ineffective in providing neuroprotection for the stroke affected areas and also fall outside the clinical time window.