Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood
Authors: Broadwell Richard Dow , Brightman Milton W. 
Published: January 2005

Autonomic preganglionic, sensory, and lower motoneuron perikarya within the central nervous system, as well as cell bodies with axons projecting to the circumventricular organs, are retrogradely labeled with horseradish peroxidase (HRP) delivered to their axon terminals by cerebral and extracerebral blood. Subsequent to vascular injection of HRP into mice, blood‐borne peroxidase passes across permeable vessels in muscle, ganglia, and in all circumventricular organs except for the subcommissural organ in which no leak could be discerned. Brain parenchyma adjacent to each of the permeable circumventricular organs quickly becomes inundated with the protein. By four to six hours post‐injection, this extracellular HRP reaction product has disappeared, and by eight hours perikarya of specific hypothalamic nuclei contain HRP‐positive granules indicative of the intra‐axonal retrograde transport of the protein. Hypothalamic neurons so labeled are presumed to send axons to such circumventricular organs as the median eminence or neurohypophysis and include neurons of the magnocellular neurosecretory supraoptic and paraventricular nuclei, the accessory magnocellular nuclei, the parvicellular arcuate nucleus, and a band of periventricular cells extending rostrally into the medial preoptic area. Labeled somata are also adjacent to the organum vasculosum of the lamina terminalis and in the vertical limb of the nucleus of the diagonal band of Broca. No similarly labeled cell bodies were identified near the subfornical organ.

At 12 hours post‐injection, HRP labeling of specific brain stem and spinal cord somata with axons efferent from the central nervous system indicates that protein from the peripheral blood can be incorporated by neurons of different functional categories for retrograde transport. Thus, blood‐borne peroxidase, imbibed presumably from myoneural clefts by motoneuron axon terminals, is transported to perikarya in cranial motor nerve nuclei III, IV, V, VI, VII, XII, the ambiguus nucleus, and in the ventral horn of the spinal cord. Sensory endings afferent to muscle spindles also take up HRP for retrograde transport, as manifested by the labeling of cell bodies in the mesencephalic nucleus of V. Autonomic preganglionic terminals take up HRP for transport back to their cell bodies in the intermediolateral sympathetic cell column in the spinal cord and to parasympathetic cell groups such as the brain stem dorsal motor vagus and salivatory nuclei.

Three cell groups in the brain stem that presumably have their efferent projections intrinsic to the central nervous system contain peroxidase‐labeled perikarya. These cell groups include a portion of the nucleus of the solitary tract rostral to the area postrema and the noradrenergic A1 and A5 nuclei of Dahlström and Fuxe ('64). The area postrema is thought to receive axon collaterals from the nucleus of the solitary tract (Morest, '60). Of the circumventricular organs, only the median eminence is believed to have a prominent noradrenergic innervation originating from somewhere in the brainstem. The peroxidase‐labeled A1 and A5 neurons may represent the origin of this innervation.

Vascular infusion of peroxidase results in retrograde neuronal labeling of neurosecretory, motor, sensory, and autonomic systems. The inference is made that other substances, such as toxins and neurovirulent viruses, can also enter these neuronal systems, as does peroxidase, from cerebral and extracerebral blood.