Anatomic distribution of apoptosis in medulla oblongata of infants and adults

Abstract

The aim of the study was to evaluate the distribution of apoptosis in the medullary nuclei of infants and adults who died of hypoxic-ischaemic injury. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) in brainstems from 22 adults (7 subjects who died of opiate intoxication, 15 who died of other hypoxic-ischaemic injury) and 10 infants. The nuclei examined included the hypoglossal, dorsal motor nucleus of the vagus, nucleus tractus solitarii, nucleus of the spinal trigeminal tract, cuneate, vestibular and inferior olivary nuclei. A morphometric analysis with the optical disector method was performed to calculate the mean percentages (+/- standard deviation) of TUNEL-positive neuronal and glial cells for the sample populations. Opiate deaths did not have higher apoptotic indices than other adult hypoxic-ischaemic deaths. Statistically significant differences between adults and infants were found in the neuronal apoptotic indices of the cuneate (28.2 +/- 16.3% vs. 6.9 +/- 8.7%), vestibular (24.7 +/- 15.0% vs. 11.3 +/- 11.4%), nucleus tractus solitarii (11.2 +/- 11.2% vs. 2.3 +/- 2.4%), dorsal motor nucleus of the vagus (6.8 +/- 8.5% vs. 0.1 +/- 0.2%) and hypoglossal (6.6 +/- 5.7% vs. 0.1 +/- 0.2%), indicating higher resistance of the neuronal populations of these infant medullary nuclei to terminal hypoxic-ischaemic injury or post-mortem changes. Differences in neuronal apoptotic index were also statistically significant among nuclei, suggesting differential characteristics of survival. Nuclei with higher neuronal apoptotic indices were the cuneate, vestibular and nucleus of the spinal trigeminal tract, which are located in the lateral medullary tegmentum and share the same vascular supply from the posterior inferior cerebellar artery.

Fig. 1

(A) Sketch showing varying incidence of neuronal apoptosis in medullary nuclei. (Cu, cuneate nucleus; Ve, medial vestibular nucleus; NTS, nucleus tractus solitarii; DMNV, dorsal motor nucleus of vagus; XII, hypoglossal nucleus; NSTT, nucleus of spinal trigeminal tract; PION, principal inferior olivary nucleus; MION, medial accessory inferior olivary nucleus; DION, dorsal accessory inferior olivary nucleus). (B) Histological section of medulla of an adult case at level of caudal portion of IV ventricle (Klüver-Barrera, 1X). (C) Medullary tegmentum stained by TUNEL method showing higher neuronal apoptosis incidence in Cu, Ve and NSTT, corresponding to lateral area, than in XII, DMNV and NTS. Photomicrographs (10×) mounted together by photo stitch 3.1 (Canon Inc., Lake Success, NY, USA).

Fig. 2

TUNEL-positive neurons of inferior olivary complex, showing chromatin condensation (63×).

Fig. 3

Differences in incidence of neuronal apoptosis in hypoglossal nucleus (A, 20×), dorsal motor nucleus of vagus (B, 20×), cuneate nucleus (C, 20×), medial vestibular nucleus (D, 20×), nucleus of spinal trigeminal tract (E, 20×) and principal inferior olivary nucleus (F, 20×).