Germinal matrix hemorrhage induces immune responses, brain injury, and motor impairment in neonatal rats

Abstract

Germinal matrix hemorrhage (GMH) is a major complication of prematurity that causes secondary brain injury and is associated with long-term neurological disabilities. This study used a postnatal day 5 rat model of GMH to explore immune response, brain injury, and neurobehavioral changes after hemorrhagic injury. The results showed that CD45high/CD11b+ immune cells increased in the brain after GMH and were accompanied by increased macrophage-related chemokine/cytokines and inflammatory mediators. Hematoma formed as early as 2 h after injection of collagenase VII and white matter injury appeared not only in the external capsule and hippocampus, but also in the thalamus. In addition, GMH caused abnormal motor function as revealed by gait analysis, and locomotor hyperactivity in the elevated plus maze, though no other obvious anxiety or recognition/memory function changes were noted when examined by the open field test and novel object recognition test. The animal model used here partially reproduces the GMH-induced brain injury and motor dysfunction seen in human neonates and therefore can be used as a valid tool in experimental studies for the development of effective therapeutic strategies for GMH-induced brain injury.

Recent advances in mechanistic, therapeutic, and diagnostic research of cerebrovascular diseases: updates from brain & BrainPET 2022

“…7 Neuroinflammation is increasingly recognized as a critical mediator of functional decline, which can be affected by both peripheral and local inflammation. 8 Zhang et al described myeloid immune cell infiltration, increased proinflammatory signaling, extensive and widespread white matter damage, and motor deficits in the germinal matrix hemorrhage (GMH) model, 9 which is a significant complication in prematurity. Li et al focused on neuroinflammatory aspects, briefly discussing the dual actions of the stress-associated activating transcription factor 3 (Atf3) in neuroinflammatory responses after brain injury.…”

“…8 Zhang et al. described myeloid immune cell infiltration, increased proinflammatory signaling, extensive and widespread white matter damage, and motor deficits in the germinal matrix hemorrhage (GMH) model, 9 which is a significant complication in prematurity. Li et al.…”