Blood-brain-barrier disruption in chronic canine hypothyroidism.
BACKGROUND
Central nervous system (CNS) manifestations of hypothyroidism have been associated with cerebrovascular complications. Reports of cerebrospinal fluid (CSF) abnormalities are rare in hypothyroid dogs.


OBJECTIVE
The aim of this study was to determine if chronic hypothyroidism causes blood-brain-barrier (BBB) abnormalities that are detectable using indirect CSF biomarkers.


METHODS
The study included 18 normal, euthyroid, female mixed-breed dogs. Hypothyroidism was induced by (131) iodine administration in 9 dogs; 9 served as untreated controls. Evaluations included physical and neurologic examination, complete CSF analysis, serum and CSF protein electrophoresis, measurement of plasma vascular endothelial growth factor (VEGF) and serum S-100B concentrations, and calculation of CSF albumin quota (AQ) and were conducted at baseline and 6, 12, and 18 months after induction of hypothyroidism. Data were analyzed using repeated measures ANOVA.


RESULTS
At baseline, differences between groups were not detected for any variable. Throughout the study, controls dogs remained free of neurologic disease and had test variables that remained within reference intervals. Two hypothyroid dogs developed CNS signs during the study, and evidence of cerebrovascular disease was found at necropsy. At 12 and 18 months, the CSF total protein, VEGF, S-100B, and fractional albumin concentrations, and AQ were significantly higher (P<.04) in hypothyroid dogs than controls. Among test variables assayed in serum or plasma, the only significant difference was a higher S-100B concentration in hypothyroid dogs (P=.003) at 18 months.


CONCLUSIONS
BBB integrity is disrupted in chronic hypothyroidism. Significant increases in CSF concentrations of VEGF and S100-B in hypothyroid dogs indicate dysfunction in both endothelial and glial elements of the BBB.
Pancotto
Theresa
T
Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Rossmeisl
John H
JH
Panciera
David L
DL
Zimmerman
Kurt L
KL
D000818:Animals; D001812:Blood-Brain Barrier; D004283:Dog Diseases / Q000134:cerebrospinal fluid*; D004285:Dogs; D004587:Electrophoresis, Agar Gel / Q000662:veterinary; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D007037:Hypothyroidism / Q000134:cerebrospinal fluid / Q000150:complications / Q000662:veterinary*; D009414:Nerve Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000134:cerebrospinal fluid
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D042461:Vascular Endothelial Growth Factor A