1,5Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.One of the major global health care challenges today is to tackle debilitating neurological and psychiatric disorders that affect mood or emotion, and cognitive functions 1,2 . The hallmarks of these diverse brain and behaviour disorders are neurodegeneration and/or altered neuroplasticity. Recent evidence highlight compromised neurotrophic and neurogenic characteristics on one hand and heightened neuroinflammation, on the other hand, associated with many central nervous system (CNS) disorders. The mood disorders that include depression, anxiety, post-traumatic stress disorder (PTSD), etc., are chronic debilitating CNS disorders, which in the long run also appear to cause cognitive decline 3,4 . The cognitive disorders, grouped together as 'dementia' , include diseases as diverse as Alzheimer's disease, frontotemporal dementia, vascular dementia (induced by acute and chronic vascular perturbations or ischemic stroke), etc., and are progressively neurodegenerative in nature [5][6][7] . Another debilitating neurodegenerative condition is the cerebral ischemic stroke and the resultant vascular dementia cases are approaching an alarming level worldwide largely due to the lifestyle changes 8,9 . Acute ischemic stroke is one of the leading causes of death and long-term disability and the most unfortunate thing is the limited therapeutic
