Traumatic Injury in vitro Elicits JNK-mediated Human Astrocyte Retraction, but Spares Cerebrovascular Endothelial Cells
Year: 2013
Type: article
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).\nCI 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.\nThese 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.
Author: Claudia Augustine
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W142561214