Suppression of thalamocortical oscillations following traumatic brain injury in rats

Laboratory investigation

Chris Kao M.D., Ph.D.1, Jonathan A. Forbes M.D.1, Walter J. Jermakowicz Ph.D.2, David A. Sun M.D., Ph.D.5, Brandon Davis M.D., Ph.D.1, Jiepei Zhu M.D., Ph.D.6, Andre H. Lagrange M.D., Ph.D.3,4, and Peter E. Konrad M.D., Ph.D.1
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  • 1 Department of Neurological Surgery, Vanderbilt University Medical Center,
  • | 2 Vanderbilt University School of Medicine;
  • | 3 Department of Neurology, Tennessee Valley Veterans Administration;
  • | 4 Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee;
  • | 5 Department of Neurosurgery, Norton Neuroscience Institute, Louisville, Kentucky; and
  • | 6 Department of Anesthesiology, Virginia Commonwealth University, Richmond, Virginia
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Object

Traumatic brain injury (TBI) often causes an encephalopathic state, corresponding amplitude suppression, and disorganization of electroencephalographic activity. Clinical recovery in patients who have suffered TBI varies, and identification of patients with a poor likelihood of functional recovery is not always straightforward. The authors sought to investigate temporal patterns of electrophysiological recovery of neuronal networks in an animal model of TBI. Because thalamocortical circuit function is a critical determinant of arousal state, as well as electroencephalography organization, these studies were performed using a thalamocortical brain slice preparation.

Methods

Adult rats received a moderate parietal fluid-percussion injury and were allowed to survive for 1 hour, 2 days, 7 days, or 15 days prior to in vitro electrophysiological recording. Thalamocortical brain slices, 450-μm thick, were prepared using a cutting angle that preserved reciprocal connections between the somatosensory cortex and the ventrobasal thalamic complex.

Results

Extracellular recordings in the cortex of uninjured control brain slices revealed spontaneous slow cortical oscillations (SCOs) that are blocked by (2R)-amino-5-phosphonovaleric acid (50 μM) and augmented in low [Mg2+]o. These oscillations have been shown to involve simultaneous bursts of activity in both the cortex and thalamus and are used here as a metric of thalamocortical circuit integrity. They were absent in 84% of slices recorded at 1 hour postinjury, and activity slowly recovered to approximate control levels by Day 15. The authors next used electrically evoked SCO-like potentials to determine neuronal excitability and found that the maximum depression occurred slightly later, on Day 2 following TBI, with only 28% of slices showing evoked activity. In addition, stimulus intensities needed to create evoked SCO activity were elevated at 1 hour, 2 days, and 7 days following TBI, and eventually returned to control levels by Day 15. The SCO frequency remained low throughout the 15 days following TBI (40% of control by Day 15).

Conclusions

The suppression of cortical oscillatory activity following TBI observed in the rat model suggests an injury-induced functional disruption of thalamocortical networks that gradually recovers to baseline at approximately 15 days postinjury. The authors speculate that understanding the processes underlying disrupted thalamocortical circuit function may provide important insights into the biological basis of altered consciousness following severe head injury. Moreover, understanding the physiological basis for this process may allow us to develop new therapies to enhance the rate and extent of neurological recovery following TBI.

Abbreviations used in this paper:

ACSF = artificial CSF; EEG = electroencephalographic; SCO = slow cortical oscillation; TBI = traumatic brain injury.

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