Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. Douglas D. Fraser

Abstract

The pathophysiology of a traumatic brain injury (TBI) involves the dysfunction of the blood-brain barrier (BBB). The lumen of the BBB is lined with cerebrovascular endothelial cells (CVEC) that are ensheathed with perivascular astrocyte endfeet. We investigated the cellular response of human-astrocytes and human-CVEC following trauma in vitro. Astrocytes and CVEC were subjected to a concussive injury (CI; mechanical stretch), then assessed for markers of injury (monolayer retraction) and activation (mitogen-activated protein kinases (MAPK) phosphorylation).

CI induces astrocyte monolayer retraction and activation, with predominant phosphorylation of JNK1/2 MAPK. Interfering with JNK1/2 activation (selective JNK inhibitors) reduces trauma-induced astrocyte retraction. On the contrary, CI does not induce CVEC retraction, however up-regulates CVEC pro-adhesive phenotype resulting in increased polymorphonuclear leukocyte (PMN) adhesion.

These findings indicate that CI elicits differential BBB cell responses: JNK-mediated astrocyte retraction and CVEC-dependent increase in leukocyte recruitment, the phenomena that may contribute to overall BBB dysfunction following TBI.


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Physiology Commons

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