Vascular Dementia

In humans there are 13 established members of the aquaporin (AQP) membrane protein water channels (AQP0-12) with a further two possible members recently discovered (AQP 13 & 14). AQPs are distributed throughout a wide range of tissues and involved in many physiologies; they have been shown to play a role in diverse disorders and pathologies1. Consequently, AQPs have been highlighted as key drug targets2. AQPs mediate water influx during cerebral oedema following ischemia as a result of traumatic brain injury or stroke. A number of AQPs have been shown to be expressed in the brain with AQP1 and 4 the most abundant. This project aimed to identify and study the molecular tools that could manipulate the translocation of brain AQPs as promising drug targets and also understanding the mechanisms of action/resistance for mannitol; which is considered to be a mainstay and gold standard to treat brain edema in order improve its therapeutic effectiveness. Microarray on primary rat astrocytes has been used to investigate the possible mechanisms involved in the process of oedema under hypoxic and/or normoxic conditions. qRT-PCR was used to confirm the transcriptional capacity of the genes of interest from the microarray data. Potential key proteins within suggested mechanistic pathways were identified through analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID).