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

Abstract

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 (PbtO), 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, PbtO, 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 PbtO and [Lac]b, followed by prolonged decline. Recovery of PbtO 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.

Neurometabolic and electrophysiological changes during cortical spreading depolarization: multimodal approach based on a lactate-glucose dual microbiosensor arrays

“…In spite of some differences in the magnitude of the changes and the temporal profile, the variations in lactate and glucose here reported followed the known metabolic signature of SD, globally characterized by a fall in glucose extracellular concentration and an increase in lactate 5–9 . The significant drop in glucose concentration occurs due to glycolysis stimulation in response to a massive increase in oxidative phosphorylation to generate the ATP required to restore the ionic gradients lost during the SD wave.…”

An implantable multimodal sensor for oxygen, neurotransmitters, and electrophysiology during spreading depolarization in the deep brain

“…26, 52, 53 For these reasons, amperometry is widely used to measure in vivo oxygen. 17, 26, 54, 55 Therefore, we employed amperometry to confirm that oxygen currents were devoid of interference.…”

“…14 Thus, many current methodologies rely on multiple invasive sensors that may contribute to tissue damage. 15–17 Improved, single-implant devices recently detected simultaneous changes of glucose and lactate in real time. 18, 19 However, these sensors do not provide parallel electrophysiological measurements, which verify SD.…”

Microelectrode Biosensors for in vivo Analysis of Brain Interstitial Fluid

“…Recently, a more complete view of brain metabolism has been obtained with simultaneous monitoring of O 2 , glucose, and lactate concentrations by using microelectrodes, and with the use of cerebral perfusion and laser Doppler flowmetry . In particular, the effects of spreading depolarization on brain metabolism have been carefully assessed.…”