Extracellular Brain Ph with or without Hypoxia is a Marker of Profound Metabolic Derangement and Increased Mortality after Traumatic Brain Injury

Abstract

Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pH bt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pH bt and P bt O 2 : 1-low P bt O 2 /pH bt , 2-low pH bt /normal P bt O 2 , 3-normal pH bt /low P bt O 2 , and 4-normal pH bt /P bt O 2 ). Microdialysis values were compared between the groups. The relationship between P bt O 2 and lactate/pyruvate (LP) ratio was evaluated at different pH bt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1-higher LP and reduced glucose (Po0.001). A significant negative correlation between LP and P bt O 2 (rho ¼ À 0.159, Po0.001) was stronger at low pH bt (rho ¼ À 0.201, Po0.001) and nonsignificant at normal pH bt (P ¼ 0.993). The state 2 was a significant discriminator of mortality categories (P ¼ 0.031). Decreased pH bt is associated with impaired metabolism. Measuring pH bt with P bt O 2 is a more robust way of detecting metabolic derangements.

Protons Regulate Vesicular Glutamate Transporters through an Allosteric Mechanism

“…Thus, transporter at the plasma membrane is inactivated under physiological conditions. Ischemia or traumatic brain injury that reduce extracellular pH may therefore promote glutamate efflux and excitotoxicity through this mechanism (McDonald et al, 1998; Chesler, 2003; Timofeev et al, 2013). …”

Excitotoxicity and Metabolic Crisis Are Associated with Spreading Depolarizations in Severe Traumatic Brain Injury Patients

“…Increases in the LPR, an established marker of metabolic crisis that signals a switch from aerobic to anaerobic metabolism due to ischemia and/or mitochondrial dysfunction, 7,8 were initially thought to reflect secondary hypoxic/ischemic events. 5,6,[8][9][10][11][12] However, recent reports have shown these perturbations are more enigmatic, as severe metabolic crisis (LPR >40) is observed even after adequate resuscitation, 13 in the absence of frank ischemia, 14 and independent of cerebral perfusion pressures. 15 Vespa and colleagues have shown that non-convulsive seizures are one pathophysiological source of such a non-ischemic ''metabolic crisis.''…”

Unveiling a hidden 31P signal coresonating with extracellular inorganic phosphate by outer‐volume‐suppression and localized 31P MRS in the human brain at 7T

“…Such measurements in humans have been challenging technically but are critical for understanding normal brain processes, as well as the pathophysiology of a variety of brain conditions and diseases such as tumors and traumatic brain injury. [5][6][7][8][9][10][11][12][13][14]…”