Hypoxic-ischemic encephalopathy remains a significant cause of neonatal morbidity and mortality in neonates. Our study tested whether intranasal insulin provides long-term neuroprotection against neonatal hypoxia–ischemia (HI)-induced hippocampal damage and cognitive disturbances in juvenile rats. Postnatal day 10 (P10) Sprague-Dawley rats underwent right common carotid artery ligation or sham surgery followed by 90 min of hypoxia (8% oxygen) or room air, respectively. Immediately after, insulin (25 μg) or vehicle was administered in each naris, followed by repeated doses 24 and 48 h post-insult. HI caused acute cerebral ATP depletion, an acute inflammatory response characterized by increased IL-1β, and corticosterone elevation. Intranasal insulin significantly attenuated ATP loss, reduced interleukin-1β and corticosterone levels, and improved somatic growth. Behaviorally, intranasal insulin protected against neonatal HI-induced sensorimotor deficits, working memory impairments, and learning deficits in both sexes of juvenile rats (P21-P25). Male pups exhibited selective long-term memory deficits following HI, which were fully rescued by intranasal insulin. Histologically, neonatal HI induced hippocampal neuronal loss and increased Fluoro-Jade C + degenerating cells, together with loss of mature NeuN + neurons in hippocampal CA3, and suppression of dentate gyrus neurogenesis, with greater loss of immature DCX + neurons in P25 male rats. HI insult also resulted in brain inflammation, as indicated by microglia activation (Iba1 + ) and serum interleukin-1β elevation. Intranasal insulin significantly reduced HI-induced brain inflammation and protected against hippocampal neuronal injury in both sexes. These findings demonstrate long-lasting neuroprotective effects of intranasal insulin following neonatal HI and support further investigation of this non-invasive approach for hypoxic-ischemic encephalopathy in neonates.
While recent studies have drawn attention to the potential role of proprioceptive dysfunction in the development of adolescent idiopathic scoliosis (AIS), its precise characterization remains incomplete. Most research has focused on static proprioception, revealing generally mild or inconsistent deficits. By contrast, dynamic muscle proprioception, particularly the ability to encode limb movement kinematics, remains largely unexplored. This study is the first to assess both static and dynamic muscle proprioception within the same body segment in severe AIS.Fifty-one AIS participants and 31 age-matched controls underwent proprioceptive assessment. Static proprioception was assessed using a knee joint position matching task, while dynamic muscle proprioception was evaluated through vibration-induced movement illusions applied to both legs. Leg movements were recorded with a 3D motion-capture system.Static position-matching performance did not differ between AIS participants and controls. By contrast, vibration-induced illusory movements revealed significant group differences: 27% of AIS participants failed to perceive movement illusions in at least one condition versus 5% of controls, and AIS participants reported reduced illusion amplitudes and velocities (p < 0.01) with moderate effect size (partial η2≈0.08). This impairment was most pronounced in single-curve AIS participants, who showed significantly lower illusion amplitudes and velocities than both controls (p < 0.001, Cohen’s d = 0.43) and double-curve AIS (p < 0.05, Cohen’s d = 0.28), whereas double-curve AIS did not differ from controls.These findings demonstrate a predominant impairment in Ia-mediated movement perception in severe AIS. The greater impairment observed in single-curve AIS indicates that muscle proprioceptive dysfunction may vary across clinical subtypes, supporting the existence of distinct sensory phenotypes in AIS.
