The Role of Oxidative Stress in the Progression of Secondary Brain Injury Following Germinal Matrix Hemorrhage

Abstract

Germinal matrix hemorrhage (GMH) can be a fatal condition responsible for the death of 1.7% of all neonates in the USA. The majority of GMH survivors develop long-term sequalae with debilitating comorbidities. Higher grade GMH is associated with higher mortality rates and higher prevalence of comorbidities. The pathophysiology of GMH can be broken down into two main titles: faulty hemodynamic autoregulation and structural weakness at the level of tissues and cells. Prematurity is the most significant risk factor for GMH, and it predisposes to both major pathophysiological mechanisms of the condition. Secondary brain injury is an important determinant of survival and comorbidities following GMH. Mechanisms of brain injury secondary to GMH include apoptosis, necrosis, neuroinflammation, and oxidative stress. This review will have a special focus on the mechanisms of oxidative stress following GMH, including but not limited to inflammation, mitochondrial reactive oxygen species, glutamate toxicity, and hemoglobin metabolic products. In addition, this review will explore treatment options of GMH, especially targeted therapy.

Keywords: Apoptosis; Germinal matrix hemorrhage; Glutamate toxicity; Inflammation; Iron toxicity; Melatonin; Oxidative stress; Reactive oxygen species; Therapeutic hypothermia.