Subplate neurons: potential targets for dysfunction after hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury (HIBI) is a leading cause of long-term neurological disability in children, often resulting in motor deficits, cognitive impairments, and behavioral abnormalities. Effective curative interventions for hypoxic-ischemic brain injury (HIBI) and its sequelae remain very limited. Recent research suggests that some disabilities are closely linked to the developmental disruption of neural circuits, characterized by aberrant thalamocortical projections, reduced network oscillatory activity, and loss of functional connectivity across brain regions. In this context, subplate neurons (SPNs), a transient but crucial population of "hub" cells during development, play a central role in coordinating neuronal migration and establishing early synaptic networks. Critically, SPNs are highly vulnerable to hypoxic-ischemic (HI) insult. Damage to SPNs not only disrupts the structural integrity of subcortical circuits but also leads to a loss of synchrony in functional networks, positioning them as a key mechanism in HIBI-related neurological dysfunction. This review focuses on the vulnerability of subplate neurons following hypoxia-ischemia and their impact on neural circuitry. Furthermore, we explore potential neuroprotective strategies targeting SPNs, offering new therapeutic perspectives and opportunities for repair to improve outcomes in HIBI.