Background: Edema represents one of the earliest negative markers of survival and consecutive
neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating
this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema,
which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative.
Objective: New insights into water metabolism in the brain have opened the way for molecular targeted
treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the
effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in
Methods: Using a permanent medial cerebral artery occlusion rat model, we administrated a single
dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily
Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations
were next performed.
Results: We showed first that the combination treatment animals have a better motor function preservation
at seven days after permanent ischemia. We have also identified distinct cellular contributions
that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronalsurvival
phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin
alone or untreated animals.
Conclusion: Our data show that water diffusion inhibition and Cerebrolysin administration after focal
ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.