Nonregenerative axonal growth within the mature mammalian brain: ultrastructural identification of sympathohippocampal sprouts

Abstract

Damage to septohippocampal neurons in the adult rat results in sprouting of sympathetic axons into the denervated hippocampal formation. However, the distribution of sympathohippocampal fibers has only been assessed with light microscopic techniques, and it is not known if the sprouted fibers leave the blood vessels, along which they migrate into the hippocampal formation, to enter the hippocampal neuropil and, if they do, whether they form synaptic contacts with central neurons. Using the tetramethylbenzidine technique to visualize anterogradely transported wheat germ agglutinin-horseradish peroxidase conjugate, we identified sprouted sympathetic fibers in the hippocampal formation at both the light and electron microscopic level in albino rats receiving medial septal lesions. The majority of labeled fibers were observed within the regions immediately above and below the granule cell layer. Although most of the labeled sprouts were observed in association with intraparenchymal blood vessels, where they were usually apposed to the basal lamina, approximately a third of the labeled profiles were present within the neuropil with no obvious vascular relationships. Most of the profiles were identified as unmyelinated axons or vesicle-filled varicosities. Many of the latter structures contained small dense-cored vesicles, but in our sample none of the labeled profiles were observed to form membrane specializations with adjacent structures, and many were partly surrounded by presumed astrocytic processes. These results document the invasion of the CNS by sprouting axons of peripheral origin indicating that axonal elongation from uninjured neurons can occur within the mature mammalian CNS under certain circumstances. In addition, the presence of significant numbers of sympathetic fibers within the hippocampal neuropil indicates that they may be in a strategic position to influence hippocampal function.

Axonal regeneration from injured dorsal roots into the spinal cord of adult rats

“…The entry of primary sensory axons into the spinal cord around blood vessels has been recorded previously by Kozlova et al (1995), who transplanted fetal DRG cells into the dorsal roots of adult rats after removing the adult sensory neurons. Sympathetic axons growing into the brain of adult rats after section of the fimbria/fornix also enter the CNS around blood vessels (Crutcher and Marfurt, 1988) and sprouting CNS axons near regions of injury are often found around blood vessels (Campbell et al, 1992;Tew et al, 1992; unpublished observations by Roslan and Anderson of spinal cord injuries). Consequently, it would appear that the microenvironment around CNS blood vessels may be more conducive to axonal elongation than the surrounding neuropil and that vessels entering the spinal cord represent a weak point in the defences against invading peripheral axons.…”

Expression of L1 and PSA during sprouting and regeneration in the adult hippocampal formation

“…In the present study, TH-positive fibers that sprouted in NGF-producing grafts or in the denervated HF of ␤Gal-grafted animals expressed L1. Sympathetic axons sprouting in the denervated HF do not form membrane specialization resembling synaptic contacts (Crutcher and Marfurt, 1988). Therefore, L1 expression by TH-positive sprouting fibers following a lesion of the FF is unlikely to be related to synaptic stabilization.…”

“…Therefore, L1 expression by TH-positive sprouting fibers following a lesion of the FF is unlikely to be related to synaptic stabilization. Sympathetic fibers in the denervated HF are often found in fascicles (Crutcher and Marfurt, 1988) and it is probable that L1 participates in the bundling of these TH-positive fibers. Moreover, TH-positive sprouting fibers do not express PSA and this lack of PSA might promote L1-mediated adhesion, preventing these fibers from defasciculating and interacting with the environment of the HF.…”

Plasticity in the Rat Hippocampal Formation following Ibotenic Acid Lesion of the Septal Region: A Quantitative [14C]Deoxyglucose and Acetylcholinesterase Study

“…Besides promoting the growth of catecholamine-containing sympathetic fibers of the superior cervical ganglion into the hippocampal region (Loy et aI., 1980;Crutcher and Chandler, 1985;Crutcher, 1987;Crutcher and Marfurt, 1988), NGF most probablY provokes homotypic collateral sprouting of spared cholinergic projecting neurons in the hippocampus (Kromer, 1987;Gage et aI., 1988;Montero and Hefti, 1988). Unlike cholinergic septal neurons, NGF was not found to affect GABAergic septohip pocampal neurons (Blaker et aI., 1988).…”