Premium
Deficiency of telomerase activity affects the blood brain barrier disruption and neurological outcome in a model of middle cerebral artery occlusion
Author(s) -
Zhang Bei,
Chen Lei,
Swartz Karin R,
Bruemmer Dennis,
Hennig Bernhard,
Toborek Michal
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.614.3
Subject(s) - telomerase , telomere , stroke (engine) , medicine , somatic cell , telomerase reverse transcriptase , middle cerebral artery , occlusion , reverse transcriptase , wild type , biology , pathology , ischemia , gene , genetics , polymerase chain reaction , mechanical engineering , engineering , mutant
Epidemiology and genetic studies indicate that patients with telomere length shorter than average are at higher risk of dying from heart disease or stroke. Telomeres are located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during aging. The enzyme telomerase can compensate for telomere loss during cell replication. The present study is aimed to investigate the contribution of telomerase to stroke and the blood‐brain barrier (BBB) dysfunction. Telomerase reverse transcriptase knock‐out (TERT‐/‐) and wild‐type mice (males, 4‐month‐old) were subjected to permanent 24 h middle cerebral artery occlusion (MCAO). Neurological testing revealed that TERT‐/‐ mice showed enhanced deficits as compared to wild‐type animals. These changes appeared to be associated with greater infarct volume in TERT‐/‐ mice. Expression of tight junction proteins, such as ZO‐1 and ZO‐2, was decreased in ischemic hemispheres both in TERT‐/‐ and wild type mice. These results suggest that TERT deficiency can predispose to the development of stroke and diminish the recovery processes in an experimental model of this disease.