In the past several decades, bilirubin has attracted great attention for central nervous system (CNS) toxicity in some pathological conditions with severely elevated bilirubin levels. CNS function relies on the structural and functional integrity of neural circuits, which are large and complex electrochemical networks. Neural circuits develop from the proliferation and differentiation of neural stem cells, followed by dendritic and axonal arborization, myelination, and synapse formation. The circuits are immature, but robustly developing, during the neonatal period. It is at the same time that physiological or pathological jaundice occurs. The present review comprehensively discusses the effects of bilirubin on the development and electrical activity of neural circuits to provide a systematic understanding of the underlying mechanisms of bilirubin-induced acute neurotoxicity and chronic neurodevelopmental disorders.
Objectives: To systematically explore the differences in acoustic changes and healing outcomes of tympanic membranes (TMs) with pars flaccida perforation (PFP) and pars tensa perforation (PTP).
Methods:We created PFPs and PTPs of various sizes in Sprague-Dawley rats, and evaluated TM umbo velocity and hearing function using laser Doppler vibrometry and auditory brainstem response (ABR) measurement before and immediately after perforation. Two weeks later, hearing was reevaluated and TMs were investigated by immunohistochemical staining.Results: Small PFPs and PTPs did not significantly affect umbo velocity and hearing function. Large PFPs increased umbo velocity loss at low frequency (1.5 kHz) and elevated ABR thresholds within 1-2 kHz. Large PTP caused significant velocity loss at low frequencies from 1.5 to 3.5 kHz and threshold elevations at full frequencies (1-2 kHz). Two weeks after the perforation, the hearing function of rats with healed PFPs recovered completely. However, high-frequency hearing loss (16-32 kHz) persisted in rats with healed PTPs. Morphological staining revealed that no increase in the thickness and obvious increase in collagen I level of regenerated par flaccida; regenerated pars tensa exhibited obvious increase in thickness and increased collagen I, while the collagen II regeneration was limited with discontinuous and disordered structure in regenerated pars tensa.
Conclusion:The hearing loss caused by large PFP limits at low frequencies while large PTP can lead to hearing loss at wide range frequencies. PFP and PTP have different functional outcomes after spontaneous healing, which is determined by the discrepant structure reconstruction and collagen regeneration.
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