Longitudinal changes of structural connectivity in traumatic axonal injury

Published online before print August 3, 2011, doi: 10.1212/WNL.0b013e31822c61d7 Neurology WNL.0b013e31822c61d7

1. J.Y. Wang, PhD,
2. K. Bakhadirov, MD,
3. H. Abdi, PhD,
4. M.D. Devous Sr., PhD,
5. C.D. Marquez de la Plata, PhD,
6. C. Moore, MA,
7. C.J. Madden, MD and
8. R. Diaz-Arrastia, MD, PhD

+ Author Affiliations

1.     From the Department of Cognition and Neuroscience (J.Y.W., K.B., H.A., M.D.D.) and Center for Brain Health (C.D.M.d.l.P.), University of Texas at Dallas, Richardson; and Departments of Radiology (H.A., M.D.D.), Neurology (C.M., R.D.-A.), and Neurosurgery (C.J.M.), University of Texas Southwestern Medical Center, Dallas. Dr. Diaz-Arrastia is currently with the Center for Neuroscience and Regenerative Medicine, Uniformed Services University for the Health Sciences, Rockville, MD.

1. Address correspondence and reprint requests to Dr. Ramon Diaz-Arrastia, Center for Neuroscience and Regenerative Medicine, Uniformed Services University for the Health Sciences, 12725 Twinbrook Parkway, Rockville, MD 20852 Ramon.Diaz-Arrastia@usuhs.mil

Abstract

Objectives: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome.

Methods: The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0–9 days postinjury for acute scans and 6–14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used.

Results: Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function.

Conclusions: Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome.

• Received December 13, 2010.
• Accepted March 22, 2011.

Blast-induced phenotypic switching in cerebral vasospasm

1. Patrick W. Alford¹,
2. Borna E. Dabiri,
3. Josue A. Goss,
4. Matthew A. Hemphill,
5. Mark D. Brigham, and
6. Kevin Kit Parker²

+ Author Affiliations

1.      Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard School of Engineering and Applied Science, Pierce Hall #321, 29 Oxford Street, Cambridge, MA 02138

1.      Edited* by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 20, 2011 (received for review April 14, 2011)

Abstract

Vasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased incidence. Here, using theoretical and in vitro models, we show that a single rapid mechanical insult can induce vascular hypercontractility and remodeling, indicative of vasospasm initiation. We employed high-velocity stretching of engineered arterial lamellae to simulate the mechanical forces of a blast pulse on the vasculature. An hour after a simulated blast, injured tissues displayed altered intracellular calcium dynamics leading to hypersensitivity to contractile stimulus with endothelin-1. One day after simulated blast, tissues exhibited blast force dependent prolonged hypercontraction and vascular smooth muscle phenotype switching, indicative of remodeling. These results suggest that an acute, blast-like injury is sufficient to induce a hypercontraction-induced genetic switch that potentiates vascular remodeling, and cerebral vasospasm, in bTBI patients.