Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats

J Cereb Blood Flow Metab. 2017 May;37(5):1670-1686. doi: 10.1177/0271678X16657571. Epub 2016 Jan 1.


Spreading depolarizations are waves of near-complete breakdown of neuronal transmembrane ion gradients, free energy starving, and mass depolarization. Spreading depolarizations in electrically inactive tissue are associated with poor outcome in patients with traumatic brain injury. Here, we studied changes in regional cerebral blood flow and brain oxygen (PbtO2), glucose ([Glc]b), and lactate ([Lac]b) concentrations in rats, using minimally invasive real-time sensors. Rats underwent either spreading depolarizations chemically triggered by KCl in naïve cortex in absence of traumatic brain injury or spontaneous spreading depolarizations in the traumatic penumbra after traumatic brain injury, or a cluster of spreading depolarizations triggered chemically by KCl in a remote window from which spreading depolarizations invaded penumbral tissue. Spreading depolarizations in noninjured cortex induced a hypermetabolic response characterized by a decline in [Glc]b and monophasic increases in regional cerebral blood flow, PbtO2, and [Lac]b, indicating transient hyperglycolysis. Following traumatic brain injury, spontaneous spreading depolarizations occurred, causing further decline in [Glc]b and reducing the increase in regional cerebral blood flow and biphasic responses of PbtO2 and [Lac]b, followed by prolonged decline. Recovery of PbtO2 and [Lac]b was significantly delayed in traumatized animals. Prespreading depolarization [Glc]b levels determined the metabolic response to clusters. The results suggest a compromised hypermetabolic response to spreading depolarizations and slower return to physiological conditions following traumatic brain injury-induced spreading depolarizations.

Keywords: Biosensors; brain metabolism; brain trauma; cerebral blood flow; energy metabolism; spreading depolarization; spreading depression.

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Cortical Spreading Depression / physiology*
  • Energy Metabolism / physiology*
  • Glucose / metabolism
  • Lactic Acid / metabolism
  • Male
  • Oxygen / metabolism
  • Rats, Wistar


  • Lactic Acid
  • Glucose
  • Oxygen