An inhibitor of injury-induced COX-2 transcriptional activation elicits neuroprotection in a brain damage model

Abstract

The quest to understand the molecular changes in brain injury is providing new ideas that might lead to more effective therapeutic approaches. Early molecular events in brain injury, such as the hydrolysis of membrane phospholipids, can trigger cascades of events which may constitute decision pathways leading to neuronal damage or cell death, or conversely to repair and regeneration. The fundamental problems are to identify which second messengers accumulate, the signals that trigger their production and the pathways that, in turn, they affect in the damaged regions of the brain. In the design of more discriminating pharmacological approaches it is important to understand how intervention at a single point in a signalling pathway will affect the complex web of cellular communications between neurones, and between the neurone, glia and cerebral microvasculature. While the short term survival of the subject in the acute phase of stroke, head injury or epilepsy is obviously of paramount importance, an understanding of the mechanisms which lead to the alterations in synaptic circuitry involved in delayed neurobehavioural disorders such as post-traumatic epilepsy, delayed amnesia, psychosis and dementia could help in designing therapies which promote better long-term recovery.