Ischemic stroke represents an increasing cause of mortality and disability with the continuous increasing age of the population.
The current project proposes first of all to shed more light on the relation between brain edema and glutamate-induced neurotoxicity during stroke utilizing an animal model of ischemic stroke. This evaluation will be performed based on correlating clinical recovery and evolution with the neuropathological data. In this endeavor, we will use here a classical middle cerebral artery occlusion rat model of stroke.
Second, we intend to test a new bimodal treatment protocol aiming at enhancing glutamate uptake and reducing edema formation in the initial phases of stroke. Recently, our team has showed a close structural and functional relativity between aquaporin 4 and glutamate transporter 1 (GLT-1) in the perineuronal compartment, as the most important gateways of water and glutamate buffering in the brain; and thus it would be of interest to see their combined effect compared with the individual treatments. The great simplicity of the treatment relies in the fact that both active drugs are inexpensive, and more, the GLT-1 upregulator is a classical antibiotic.
Third, as there is a complete lack of whole-brain microscopic resolution imaging in stroke, we propose here to take advantage of a revolutionary whole-organ clearing technology for unprecedented integrative and continuous volumetric data on the infarct core, penumbra, and the surrounding tissue.