Mechanisms of Perinatal Brain Injury: Preclinical Models, Acute Pathophysiology, and Neuroprotective Strategies

Perinatal brain injury, encompassing hypoxic-ischemic encephalopathy (HIE), extreme prematurity-related white matter injury, perinatal stroke, and infection-sensitized brain damage, remains a leading cause of neonatal mortality and lifelong neurological disability. While therapeutic hypothermia has significantly improved outcomes for near-term and term infants with moderate-to-severe HIE, a substantial proportion of affected infants still develop adverse neurodevelopmental sequelae, and effective therapeutic interventions for preterm infants remain scarce.The pathophysiological cascade following perinatal brain injury is multifaceted, evolving from primary energetic failure to protracted secondary and tertiary phases characterized by excitotoxicity, neuroinflammation, microglial activation, oxidative stress, mitochondrial impairment, and blood-brain barrier dysfunction. Unraveling these underlying cellular and molecular pathways in developmentally appropriate preclinical models is essential to identifying actionable therapeutic targets and designing adjuvant or standalone neuroprotective therapies.This Research Topic aims to bridge the gap between experimental neuroscience and early-phase clinical translation in perinatal brain injury. The primary objective is to deepen the mechanistic understanding of acute and subacute injury cascades and accelerate the discovery and validation of novel neuroprotective and neurorestorative strategies.By bringing together basic neuroscientists, translational researchers, neonatologists, and neuropharmacologists, this collection will highlight mechanistic insights derived from cellular systems, ex vivo preparations, and well-characterized preclinical animal models (including small and large animal paradigms of hypoxia-ischemia, inflammation, and preterm injury). The ultimate goal is to delineate critical therapeutic windows and advance safe, targeted interventions that preserve neural integrity and promote regenerative repair in the developing central nervous system.Scope and Information for AuthorsWe welcome submissions of Original Research, Reviews, Systematic Reviews, Mini Reviews, Brief Research Reports, and Methods articles. We particularly encourage studies employing rodent, piglet, sheep, non-human primate, or advanced organoid/in vitro models that address molecular, cellular, and pharmacological mechanisms of injury and repair.Submissions may address, but are not limited to, the following themes:• Cellular & Molecular Cascades: Pathophysiology of primary, secondary, and tertiary injury, including excitotoxicity, oxidative stress, mitochondrial failure, cell death pathways (apoptosis, necroptosis, ferroptosis), and autophagy in the immature brain.• Neuroinflammation & Immune Responses: The role of resident microglia, reactive astrocytes, systemic immune cell infiltration, cytokine signaling, and maternal/fetal immune activation in exacerbating or resolving perinatal brain damage.• Vascular & Barrier Dysfunction: Mechanisms of blood-brain barrier disruption, cerebral autoregulation failure, and neurovascular unit impairment following hypoxia-ischemia or perinatal stroke.• White Matter Vulnerability & Repair: Oligodendrocyte progenitor cell maturation arrest, dysmyelination, axonal injury, and remyelination strategies in preterm and term injury models.• Novel Pharmacotherapies & Adjuvant Interventions: Preclinical evaluation of neuroprotective agents, including anti-inflammatory compounds, antioxidants, gases (e.g., xenon, hydrogen), erythropoietin, melatonin, and metabolic enhancers, both as monotherapies and in combination with therapeutic hypothermia.• Regenerative & Cell-Based Therapies: Stem cell transplantation, extracellular vesicles, exosomes, and secretome-derived therapies aimed at structural repair and functional neurorestoration.• Translational Biomarkers of Acute Injury: Molecular, biochemical, and early electrophysiological correlates of tissue damage that validate target engagement and therapeutic efficacy in preclinical paradigms. Topic editors: Jing Ju, Elizabeth Harris Source: https://www.frontiersin.org/research-topics/85983/mechanisms-of-perinatal-brain-injury-preclinical-models-acute-pathophysiology-and-neuroprotective-strategies