Submit Manuscript  

Article Details


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

[ Vol. 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* and Dafin Fior Muresanu   Pages 299 - 308 ( 10 )

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.

Keywords:

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

Affiliation:

Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, Department of Physical Medicine and Rehabilitation, University of Medicine and Pharmacy of Craiova, Craiova, Department of Human Anatomy, University of Medicine and Pharmacy of Craiova, Craiova, Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, Department of Clinical Neurosciences, University of Medicine and Pharmacy “Iuliu Hatieganu” and “RoNeuro” Institute for Neurological Research and Diagnostic, Cluj-Napoca, Department of Neurology, University of Medicine and Pharmacy of Craiova, Craiova, Department of Clinical Neurosciences, University of Medicine and Pharmacy “Iuliu Hatieganu” and “RoNeuro” Institute for Neurological Research and Diagnostic, Cluj-Napoca, Department of Human Anatomy, University of Medicine and Pharmacy of Craiova, Craiova, Department of Neurology, University of Medicine and Pharmacy of Craiova, Craiova, Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, 200349, Craiova, Dolj, Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, 200349, Craiova, Dolj, Department of Clinical Neurosciences, University of Medicine and Pharmacy

Graphical Abstract:



Read Full-Text article