A model of metabolic supply-demand mismatch leading to secondary brain injury

Abstract

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin-Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI, and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be non-ischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures and SBI.

Clinical Impact of Standardized Interpretation and Reporting of Multimodality Neuromonitoring Data

“…Clinical interventions such as hemicraniectomy and the use of external ventricular drainage (EVD) catheters were similar. In univariate analysis, there were significant differences in the number of times hyperosmotic agents were used per patient (6 [1-8] for controls vs. 3 [1][2][3][4][5][6] for cases; p = 0.04) and in the proportion of hospital days in which anesthetics were used (67% [33-91%] of controls vs. 48% [24-70%] of cases; p = 0.02). The length of ICU and hospital stays were similar between cohorts.…”

Electroencephalography as a Biomarker of Prognosis in Acute Brain Injury

“…[37][38][39] These data, in addition to multimodality monitoring studies showing increased metabolic demand (reduction of brain tissue oxygenation, increase cerebral blood flow, and increase in cerebral perfusion pressure) associated with RPPs, 41 support the hypothesis that not only the presence of EAs but increased EA burden is associated with secondary brain injury due to the metabolic supply-demand mismatch. 42…”