Erez Hanael, Shelly Baruch, Rotem Kalev Altman, Orit Chai, Kira Rapoport, Dana Peery, Alon Friedman, Merav H. Shamir
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Abstract
Background
Epilepsy in dogs and humans is associated with blood-brain barrier (BBB) dysfunction (BBBD), which may involve dysfunction of tight junction (TJ) proteins, matrix metalloproteases, and astrocytes. Imaging techniques to assess BBB integrity, to identify potential treatment strategies, have not yet been evaluated in veterinary medicine.
Hypothesis
Some dogs with idiopathic epilepsy (IE) will exhibit BBBD. Identifying BBBD may improve antiepileptic treatment in the future.
Animals
Twenty-seven dogs with IE and 10 healthy controls.
Methods
Retrospective, prospective cohort study. Blood-brain barrier permeability (BBBP) scores were calculated for the whole brain and piriform lobe of all dogs by using dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) and subtraction enhancement analysis (SEA). Matrix metalloproteinase-9 (MMP9) activity in serum and cerebrospinal fluid (CSF) was measured and its expression in the piriform lobe was examined using immunofluorescent staining. Gene expression of TJ proteins and astrocytic transporters was analyzed in the piriform lobe.
Results
The DCE-MRI analysis of the piriform lobe identified higher BBBP score in the IE group when compared with controls (34.5% vs 26.5%; P = .02). Activity and expression of MMP9 were increased in the serum, CSF, and piriform lobe of IE dogs as compared with controls. Gene expression of Kir4.1 and claudin-5 in the piriform lobe of IE dogs was significantly lower than in control dogs.
Conclusions and Clinical Importance
Our findings demonstrate BBBD in dogs with IE and were supported by increased MMP9 activity and downregulation of astrocytic potassium channels and some TJ proteins. Blood brain barrier dysfunction may be a novel antiepileptic therapy target.
期刊介绍：
The mission of the Journal of Veterinary Internal Medicine is to advance veterinary medical knowledge and improve the lives of animals by publication of authoritative scientific articles of animal diseases.
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