Cerebrolysin and Aquaporin 4 Inhibition Improve Pathological and Motor Recovery after Ischemic Stroke

Title:Cerebrolysin and Aquaporin 4 Inhibition Improve Pathological and Motor Recovery after Ischemic Stroke

Volume: 17 Issue: 4

Author(s): Bogdan Catalin, Otilia-Constantina Rogoveanu, Ionica Pirici, Tudor Adrian Balseanu, Adina Stan, Valerica Tudorica, Maria Balea, Ion Mindrila, Carmen Valeria Albu, Guleed Mohamed, Daniel Pirici*Dafin Fior Muresanu

Affiliation:

• Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, 200349, Craiova, Dolj,Romania

Keywords: Aquaporin 4, ischemic stroke, brain edema, Cerebrolysin, gliosis, non-transient infarct.

Abstract: 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 ischemic stroke.

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.

Cite this article as:

Catalin Bogdan , Rogoveanu Otilia-Constantina, Pirici Ionica , Balseanu Adrian Tudor, Stan Adina , Tudorica Valerica, Balea Maria , Mindrila Ion , Albu Valeria Carmen, Mohamed Guleed , Pirici Daniel *, Muresanu Fior Dafin , Cerebrolysin and Aquaporin 4 Inhibition Improve Pathological and Motor Recovery after Ischemic Stroke, CNS & Neurological Disorders - Drug Targets 2018; 17 (4) . https://dx.doi.org/10.2174/1871527317666180425124340