Early disruptions of the blood–brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats

DiNapoli, Vincent A.; Huber, Jason D.; Houser, Kimberly; Li, Xinlan; Rosen, Charles L.

doi:10.1016/j.neurobiolaging.2006.12.007

« Previous Next »Neurobiology of Aging
Volume 29, Issue 5 , Pages 753-764, May 2008

Early disruptions of the blood–brain barrier may contribute to exacerbated neuronal damage and prolonged functional recovery following stroke in aged rats

Vincent A. DiNapoli
- Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV, USA
- The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV, USA
Jason D. Huber
- Department of Basic Pharmaceutical Sciences, West Virginia University, School of Medicine, Morgantown, WV, USA
- The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV, USA
Kimberly Houser
- Department of Basic Pharmaceutical Sciences, West Virginia University, School of Medicine, Morgantown, WV, USA
- The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV, USA
Xinlan Li
- Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV, USA
Charles L. Rosen
- Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, WV, USA
- The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, WV, USA
- Corresponding author at: Department of Neurosurgery, PO Box 9183, West Virginia University, School of Medicine, Morgantown, WV 26506-9183, USA. Tel.: +1 304 293 5041; fax: +1 304 293 4819.

Received 10 August 2006; received in revised form 4 December 2006; accepted 5 December 2006. published online 22 January 2007.

Abstract

We examined the effects of age on stroke progression and outcome in order to explore the association between blood–brain barrier (BBB) disruption, neuronal damage, and functional recovery. Using middle cerebral artery occlusion (MCAO), young (3 months) and aged (18 months) rats were assessed for BBB disruption at 20min post-MCAO, and 24h post-MCAO with tissue plasminogen activator induced reperfusion at 120min. Results showed that BBB disruptions in aged rats occurred early and increased nearly two-fold at both the 20min and 24h time points when compared to young animals. Neuronal damage in aged rats was increased two-fold as compared to young rats at 24h, while no neuronal damage was observed at 20min. Young and aged rats exhibited neurological deficits when compared to sham-controls out to 14 days following MCAO and reperfusion; however, aged rats exhibited more severe onset of deficits and prolonged recovery. Results indicate that aged rats suffer larger infarctions, reduced functional recovery and increased BBB disruption preceding observable neuronal injury.