Development of the Hair Cells of the Human Cochlea: A Scanning Electron Microscopic Study.

Introduction: In the mammalian auditory system, the cochlea is the first to attain structural and functional maturity. Although ultrastructural details of the developing cochlea of lower animals have been elucidated in the last few decades, comprehensive studies on human cochlea are lacking. Materials and Methods: In the present investigation we studied the development and maturation of the hair cells of ten human fetal cochlea from gestational weeks (GW) 12 to 37 by scanning electron microscopy. Result: We observed undifferentiated hair cells possessing numerous surface projections and long kinocilium during GW 14. At GW16, the primitive hair cells were arranged in one inner and four outer rows and had globular apices indicating the initiation of stereocilia formation. By GW 22, the globular apices were replaced by linear stereocilia and occasional kinocillia. Mature hair cells with sterocilia were observed in the basal turn at 30th week of gestation. At GW 37, the stereocilia were arranged in a typical "V" shaped pattern at the middle and apical coil, while the stereocilia of the basal turn were shorter in length resembling the adult cochlea. The inner hair cells were long and slender while outer hair cells were pear shaped, kinocilium were absent and the tunnel of Corti were well formed. Conclusion: It is concluded that in human, the morphological maturation of the hair cells starts in the basal turn around GW 22 and continues till 37th week in the apical turn indicating that early maturation of the cochlea may have a role on development of the higher auditory pathway connections.

Age-related changes in the number of cresyl-violet-stained, parvalbumin and NMDAR 2B expressing neurons in the human spiral ganglion.

Animal-studies associate age-related hearing loss (presbycusis) with decreasing number of spiral ganglion neurons (SGNs) in Rosenthal's canal (RC) of cochlea. The excitatory neurotransmitter for SGNs is glutamate (through its receptor NMDAR 2B), which can be neurotoxic through Ca2+ overload. Neurotoxicity is balanced by calcium-binding proteins (CBPs) like Parvalbumin (PV), which is the predominant CBP of the SGNs. To estimate the volume of the RC and total number of SGNs that are immunoreactive to PV and NMDAR 2B, we used unbiased stereology in 35 human cochleae derived from cadavers of persons from 2nd to 8th decade of life (subsequently statistically divided into two groups) and compared them to the total number of cresyl violet (CV) stained SGNs. We also estimated the volume of individual neurons and their nuclei. Regression analysis was made on estimated parameters against age. Hierarchical-cluster analysis was done on the neuronal against neuronal nuclear volumes.The average volume of the RC did not change with increasing age (p = 0.4115). The total number of SGNs (CV-stained and those separately expressing PV and NMDAR 2B) significantly decreased with age (p < 0.001). We identified three distinct populations of neurons on the basis of their volumes among SGNs. Thus, there is significant age-related decline in the total number of SGNs, which starts early in life. It may be due to ambient noise and inadequate neutralisation of excitotoxicity.

Morphological development of the human cochlear nucleus.

Morphological studies in developing brain determine critical periods of proliferation, neurogenesis, gliogenesis, and apoptosis. During these periods both intrinsic and extrinsic pathological factors can hamper development. These time points are not available for the human cochlear nucleus (CN). We have used design-based stereology and determined that 18-22 weeks of gestation (WG) are critical in the development of the human CN. Twenty-three fetuses and seven postnatal brainstems were processed for cresyl violet (CV) staining and immunoexpression of NeuN (neurons), GFAP (astrocytes), Ki-67 (proliferation) and TUNEL (apoptosis) and 3-D reconstruction. The volume of CN, total number of neurons selected profiles and the volume of neurons and their nuclei were estimated. Data were grouped (G) into: G1:18-20 WG, G2: 21-24 WG, G3: 25-28 WG and G4 >29 WG. The dimensions of morphologically identified neurons were also measured. The CN primordium was first identifiable at 10WG. Definitive DCN (Dorsal cochlear nucleus) and VCN (ventral cochlear nucleus) were identifiable at 16 WG. There was a sudden growth spurt in total volume of CN, number of neurons and astrocytes from 18 WG. We also observed an increase in proliferation and apoptosis after 22 WG. The number of neurons identifiable by CV was significantly lower than that by NeuN-immunostaining till 25 WG (p = 0.020), after which, both methods were equivalent. Eight morphological types of neurons were identifiable by 26 WG and could be resolved into four clusters by volume and diameter. The CN changed orientation from small, flat and horizontal at 10-16 WG to larger and oblique from 18WG onwards. Prevention of exposure to noxious factors at 18-22 WG may be important in preventing congenital deafness.