Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: A double fluorescent tracer study in the rat

Abstract

The ability of axonal regeneration of identified adult basal forebrain (BFB) neurons was examined after homotopic grafting of fetal neocortical tissue to a lesion cavity in the frontal neocortex. Using a four step experimental procedure, adult rats first received an injection of the fluorescent dye Fluoro-Gold (FG) into the sensorimotor cortex in order to label those neurons with projections to the area by retrograde axonal transport. After one week the injection area was removed by aspiration, leaving a cavity in the neocortex. One week later a block of fetal (E14) frontal cortical tissue was placed in the cavity. The animals were then allowed to survive for 6 weeks before a second fluorescent tracer, Nuclear Yellow (NY), was injected into the transplant. The animals were sacrificed 24 h later and analyzed by fluorescence microscopy. Both single labeled, FG and NY containing neurons and double labeled neurons containing both tracers were found in the BFB. The results demonstrate that adult BFB neurons can reestablish cortical projections into fetal cortical grafts (double labeled neurons), and they suggest that other BFB neurons, not initially innervating the lesioned cortical area, have sprouted into the transplant (NY labeled neurons).

Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

“…Grafting cells into cerebral cortex lesion cavities has indicated that cells can survive and develop new connections. Several papers have demonstrated that developing cells can be grafted into rodent TBIs (Castro et al, 1987 , 1988 ; Girman and Golovina, 1988 ; Kolb et al, 1988 ; Sorensen et al, 1990 ). Engraftment of pluripotent stem cell-derived neural cells or even mesenchymal stem cells or bone marrow mononuclear cells into cortical lesions has also been studied in rodents (Gaillard et al, 2007 ; de Freitas et al, 2012 ; Espuny-Camacho et al, 2013 ; Tajiri et al, 2013 ; de Freitas et al, 2015 ; Michelsen et al, 2015 ).…”

Late-Stage Immature Neocortical Neurons Reconstruct Interhemispheric Connections and Form Synaptic Contacts with Increased Efficiency in Adult Mouse Cortex Undergoing Targeted Neurodegeneration

“…In many examples of transplantation to the adult cortex using embryonic neurons, either as cell suspensions or as blocks of tissue, investigators have often reported afferent connections to the transplanted cells but no evidence for efferent connections back to the recipient brain (Gonzalez and Sharp, 1987;Gates et al, 2000a). Reports of the extent of efferent connectivity from the graft to recipient tissue have varied widely, from no efferent projections (Gonzalez and Sharp, 1987;Schulz et al, 1993;Grabowski et al, 1995) to sparse or moderate (Bermudez-Rattoni et al, 1987;Isacson et al, 1988;Kelche et al, 1988;Escobar et al, 1989;Sofroniew et al, 1990;Sørensen et al, 1990Sørensen et al, , 1996Fernandez-Ruiz et al, 1991;Isacson and Sofroniew, 1992;Schulz et al, 1993) to more extensive innervation of recipient target regions (Gibbs and Cotman, 1987;Guitet et al, 1994;Hernit-Grant and Macklis, 1996). Indeed, in many behavioral studies in which experimental animals did not show improvement after transplantation, investigators have concluded that the lack of functional recovery is most likely attributable to the lack of efferent projections from the transplanted neurons to appropriate recipient target sites.…”

Mature Astrocytes Transform into Transitional Radial Glia within Adult Mouse Neocortex That Supports Directed Migration of Transplanted Immature Neurons

“…Neocortical neurons are organized into distinct laminae and have complex axonal projections often over great distances. Following damage to the neocortex, significant functional recovery may depend critically on whether neurons can migrate into appropriate laminar locations, integrate into the host cytoarchitecture, differentiate into the appropriate type of neuron, and then reconstruct the specific disrupted local and distant projection patterns of the damaged host neurons (6,12,13,68,70,77,78).…”