Citation

Verley DR, Torolira D, Pulido B, Gutman B, Bragin A, Mayer A, Harris NG. J. Neurotrauma 2018; 35(20): 2448-2461.

Affiliation

UCLA, Neurosurgery , 10833 Le Conte Ave , Los Angeles, California, United States , 90095 ; ngharris@ucla.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5536

PMID

29717625

Abstract

Although cognitive and behavioral deficits are well known to occur following traumatic brain injury (TBI), motor deficits that occur, even after mild trauma are far less known, yet are equally persistent. This study was aimed at making progress toward determining how the brain reorganizes in response to TBI. We used the adult rat, controlled cortical impact injury model to study the ipsilesional forelimb map evoked by electrical stimulation of the affected limb, as well as the contralesional forelimb map evoked by stimulation of the unaffected limb, both before injury and at 1,2,3 and 4wks after using fMRI. End-point cFOS immunohistochemistry data following 1hr of constant stimulation of the unaffected limb were acquired in the same rats to avoid any potential confounds due to altered cerebrovascular coupling. Single and paired-pulse sensory evoked potential (SEP) data were recorded from skull electrodes over the contralesional cortex in a parallel series of rats before injury and at 3d, 1,2,3, and 4wks after injury in order to determine whether alterations in cortical excitability accompanied reorganization of the cortical map. The results show a transient trans-hemispheric shift in the ipsilesional cortical map as indicated by fMRI, remote contralesional increases in cortical excitability that occur in spatially similar regions to altered fMRI activity and greater cFOS activation, and reduced or absent ipsilesional cortical activity chronically. The contralesional changes were also indicated by reduced SEP latency within 3d after injury, but not by BOLD fMRI until much later. Detailed interrogation of cortical excitability using paired-pulse electrophysiology showed that the contralesional cortex undergoes both an early and a late post-injury period of hyper-excitability in response to injury, interspersed by a period of relatively normal activity. From these data we postulate a cross-hemispheric mechanism by which remote cortex excitability inhibits ipsilesional activation by rebalanced cortical excitation-inhibition.

Language: en

Keywords

MRI; NEUROEXCITATION; NEUROPLASTICITY; RECOVERY; SENSORY FUNCTION