Type 1 diabetes exacerbates blood-brain barrier alterations during experimental epileptic seizures in an animal model

Cell Biochem Funct. 2015 Jul;33(5):285-92. doi: 10.1002/cbf.3113. Epub 2015 May 25.

Abstract

The aim of this study was to perform the effects of diabetes on the permeability of the blood-brain barrier (BBB) during pentylenetetrazole (PTZ)-induced epileptic attacks. For this propose, the animals were divided into four groups. These groups contained were intact, PTZ-treated, diabetic and PTZ-treated diabetic individuals, respectively. To evaluate the functioning of the BBB, Evans blue was used as a BBB permeability indicator, and the expressions of zonula occludens-1 and glial fibrillary acidic protein involving the functioning of the BBB were determined immunohistochemically. Also, the changes in the release of serum tumour necrosis factor-alpha and interleukin-10 and interleukin-12 were studied by using enzyme-linked immunosorbent assay method. BBB permeability in the seizures under diabetic conditions showed a considerable increase (p < 0·01) in all of the brain we studied. The immunoreactive staining intensity of zonula occludens-1 and glial fibrillary acidic protein was found reduced in the brain regions of diabetic rats (p < 0·01). However, the serum level of tumour necrosis factor-alpha increased in diabetes and diabetes + PTZ groups, and the serum level of interleukin-12 increased significantly in all experimental groups (p < 0·05). In conclusion, diabetes dramatically increases BBB damage during epileptic seizures, and it may be derived from an elevation of paracellular passage.

Keywords: GFAP; ZO-1; blood-brain barrier; cytokines; diabetes; epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Blood-Brain Barrier / chemistry
  • Blood-Brain Barrier / drug effects*
  • Convulsants / pharmacology
  • Cytokines / blood
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Female
  • Nerve Tissue Proteins / metabolism*
  • Pentylenetetrazole / pharmacology
  • Permeability
  • Rats, Wistar
  • Streptozocin
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Blood Glucose
  • Convulsants
  • Cytokines
  • Nerve Tissue Proteins
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • Streptozocin
  • Pentylenetetrazole