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.