Tenascin-C induction exacerbates post-stroke brain damage

The role of tenascin-C (TNC) in ischemic stroke pathology is not known despite its prognostic association with cerebrovascular diseases. Here, we investigated the effect of TNC knockdown on post-stroke brain damage and its putative mechanism of action in adult mice of both sexes. Male and female C57...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 2022-02, Vol.42 (2), p.253-263
Main Authors: Chelluboina, Bharath, Chokkalla, Anil K, Mehta, Suresh L, Morris-Blanco, Kahlilia C, Bathula, Saivenkateshkomal, Sankar, Sneha, Park, Jin Soo, Vemuganti, Raghu
Format: Article
Language:English
Subjects:
Animals
Blood-Brain Barrier - metabolism
Blood-Brain Barrier - pathology
Brain Injuries - metabolism
Brain Injuries - pathology
Female
Ischemic Stroke - metabolism
Ischemic Stroke - pathology
Male
Mice
Original
Tenascin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The role of tenascin-C (TNC) in ischemic stroke pathology is not known despite its prognostic association with cerebrovascular diseases. Here, we investigated the effect of TNC knockdown on post-stroke brain damage and its putative mechanism of action in adult mice of both sexes. Male and female C57BL/6 mice were subjected to transient middle cerebral artery occlusion and injected (i.v.) with either TNC siRNA or a negative (non-targeting) siRNA at 5 min after reperfusion. Motor function (beam walk and rotarod tests) was assessed between days 1 and 14 of reperfusion. Infarct volume (T2-MRI), BBB damage (T1-MRI with contrast), and inflammatory markers were measured at 3 days of reperfusion. The TNC siRNA treated cohort showed significantly curtailed post-stroke TNC protein expression, motor dysfunction, infarction, BBB damage, and inflammation compared to the sex-matched negative siRNA treated cohort. These results demonstrate that the induction of TNC during the acute period after stroke might be a mediator of post-ischemic inflammation and secondary brain damage independent of sex.
ISSN:0271-678X
1559-7016
DOI:10.1177/0271678X211056392