TY - JOUR
T1 - Vascular Neural Network Phenotypic Transformation After Traumatic Injury
T2 - Potential Role in Long-Term Sequelae
AU - Badaut, J.
AU - Bix, G. J.
N1 - Funding Information:
long-term after TBI (orange box). In jTBI, several changes in endothelial proteins (P-gp, Cav-1, and claudin-5) have been observed up to 2 months post-TBI, suggesting a phenotypic transformation in the endothelium. Early vascular dysfunction (blue box) is still ongoing for several months/years after the primary injury and contributes to decreased blood flow, metabolism, and pathological BBB. These cerebrovascular changes are possibly contributing to the absence of recovery in cognitive functions and some neurodegenerative processes observed in TBI patients Acknowledgments We thank Dane Sorensen for critical review of the manuscript and David Ajao for tissue staining of Cav-1. This study is supported in part by the NIH R01HD061946 (JB).
PY - 2014/6
Y1 - 2014/6
N2 - The classical neurovascular unit (NVU), composed primarily of endothelium, astrocytes, and neurons, could be expanded to include smooth muscle and perivascular nerves present in both the up- and downstream feeding blood vessels (arteries and veins). The extended NVU, which can be defined as the vascular neural network (VNN), may represent a new physiological unit to consider for therapeutic development in stroke, traumatic brain injury, and other brain disorders (Zhang et al., Nat Rev Neurol 8(12):711-716, 2012). This review is focused on traumatic brain injury and resultant post-traumatic changes in cerebral blood flow, smooth muscle cells, matrix, blood-brain barrier structures and function, and the association of these changes with cognitive outcomes as described in clinical and experimental reports. We suggest that studies characterizing TBI outcomes should increase their focus on changes to the VNN, as this may yield meaningful therapeutic targets to resolve posttraumatic dysfunction.
AB - The classical neurovascular unit (NVU), composed primarily of endothelium, astrocytes, and neurons, could be expanded to include smooth muscle and perivascular nerves present in both the up- and downstream feeding blood vessels (arteries and veins). The extended NVU, which can be defined as the vascular neural network (VNN), may represent a new physiological unit to consider for therapeutic development in stroke, traumatic brain injury, and other brain disorders (Zhang et al., Nat Rev Neurol 8(12):711-716, 2012). This review is focused on traumatic brain injury and resultant post-traumatic changes in cerebral blood flow, smooth muscle cells, matrix, blood-brain barrier structures and function, and the association of these changes with cognitive outcomes as described in clinical and experimental reports. We suggest that studies characterizing TBI outcomes should increase their focus on changes to the VNN, as this may yield meaningful therapeutic targets to resolve posttraumatic dysfunction.
KW - Blood-brain barrier
KW - Cerebral blood flow
KW - Juvenile traumatic injury
KW - Matrix
KW - Neurovascular unit
KW - Smooth muscle cells
KW - Traumatic brain injury
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U2 - 10.1007/s12975-013-0304-z
DO - 10.1007/s12975-013-0304-z
M3 - Article
C2 - 24323723
SN - 1868-4483
VL - 5
SP - 394
EP - 406
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 3
ER -