Disruption of the hippocampal and hypothalamic blood-brain barrier in a diet-induced obese model of type II diabetes: prevention and treatment by the mitochondrial carbonic anhydrase inhibitor, topiramate.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model
PubMed 30616618 · doi:10.1186/s12987-018-0121-6
What was done
CD-1 mice were fed either a low-fat control diet or a high-fat diet to induce obesity and type II diabetes. The researchers evaluated the preventative and therapeutic effects of topiramate (a mitochondrial carbonic anhydrase inhibitor) versus saline vehicle on blood-brain barrier (BBB) and blood-retinal barrier (BRB) permeability using radiolabeled tracers (14C-sucrose and 99mTc-albumin). They assessed body weight, blood glucose, body composition, metabolic activity, tight junction protein expression (ZO-1 and claudin-12), and markers of oxidative stress in brain tissue.
What was found
The abstract reports no numerical data or effect sizes. High-fat feeding increased entry of 14C-sucrose into the hypothalamus and hippocampus and 99mTc-albumin across the whole brain; both were attenuated by topiramate administration. Topiramate also decreased oxidative stress measures and increased expression of tight junction proteins ZO-1 and claudin-12. In the retina, high-fat diet increased tracer permeability over time, but topiramate had no protective effect on the BRB.
Why it matters
These findings suggest that mitochondrial carbonic anhydrase inhibition can mitigate obesity- and diabetes-induced cerebral microvascular disruption in mice, highlighting a potential pathway for protecting against metabolic neurovascular dysfunction.
Limits
The study is restricted to a rodent model (CD-1 mice), which cannot directly establish clinical efficacy or safety in humans. The abstract omits sample sizes (n), drug dosing, exact quantitative values, and statistical confidence intervals. Furthermore, topiramate failed to preserve the retinal barrier, and functional cognitive outcomes were not reported.
Cited by
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