Master of Science
Dr. Douglas D. Fraser
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.
Augustine, Claudia, "Traumatic Injury in vitro Elicits JNK-mediated Human Astrocyte Retraction, but Spares Cerebrovascular Endothelial Cells" (2013). Electronic Thesis and Dissertation Repository. 1411.