Anatomical and Functional Characteristics of Fetal Neocortex Transplanted into the Neocortex of Newborn or Adult Rats

Abstract

In humans, the cerebral cortex can be affected by a variety of diseases (vascular, traumatic, neurodegenerative, etc.) and, therefore, several experimental studies have been undertaken to determine to what extent transplantation of cortical neurons could prove a useful treatment for cerebral cortical damage. The purpose of this review is to give an evaluation of the different attempts of neocortical tissue transplantation which have been undertaken, mostly in rodents, during the last decade. First, we examine the functional effects of neocortical tissue transplantation in various tasks designed to assess different aspects of behavior depending upon the localization and function of the cortical area under investigation. Second, a variety of mechanisms have been proposed by which the graft would improve host behavioral capacities. Two of these are considered in this review: trophic action on the host brain and reconstruction of cortical circuitry. Most behavioral studies in rodents seem to indicate that better synaptic integration and larger functional improvements are achieved when the embryonic neocortical tissue is transplanted into immature host neocortex, i.e. in newborn recipients. Transplantation of embryonic neocortex into an adult damaged cortex seems to provide only partial functional improvement. In adult hosts, the synaptic integration of the transplanted neurons is incomplete since, in most instances, long distance projections are not re-established. It seems, therefore, that transplantation of embryonic cortex into adult hosts would prove a useful therapeutic method only if there is a possibility of neutralizing the growth inhibitory factors of the mature host CNS.

Early (E12) cortical progenitors can change their fate upon heterotopic transplantation

“…As consistently reported in studies dealing with the connectivity of embryonic cortex grafted into newborn hosts, the density of the connections established between thalamus and graft was systematically weaker than that developed between thalamus and intact cortex (Ebrahimi‐Gaillard et al ., 1994; Roger & Ebrahimi‐Gaillard, 1994; Létang et al ., 1997; Gaillard & Roger, 2000).…”

“…This study shows that cortical cells removed at E12 from the presumptive parietal area of the telencephalic vesicle and transplanted into the parietal cortex of P0 hosts develop and maintain a substantial set of reciprocal connections with the VB. These findings obtained with early embryonic cortex are in line with those of previous reports describing the existence of thalamic afferents and/or efferents of grafts of E16 embryonic cortex homotopically placed in various cortical areas (reviewed in Ebrahimi‐Gaillard et al ., 1994; Roger & Ebrahimi‐Gaillard, 1994; Létang et al ., 1997; Frappé et al ., 1999, 2001; Gaillard & Roger, 2000). In particular, grafts of E16 parietal cortex placed into the parietal cortex of P0 recipients develop a substantial set of afferent and efferent connections with the host VB (Gaillard & Roger, 2000).…”

Electrophysiological and Synaptic Characterization of Transplanted Neurons in Adult Rat Motor Cortex

“…One of these factors, considered essential by many researchers, is the formation of connections between the host and transplanted tissue. Classically, it has been reported that functional success for frontal cortical transplant following motor cortex lesion depends on trophic action on the host brain and reconstruction of cortical circuitry, which improves the performance of animals in behavioral tests like the T-maze (Labbe et al, 1983;Roger and Ebrahimi-Gaillard, 1994). Moreover, it has been shown that a lesion in the rat frontal cortex produces a deficit in the paw used in reaching tasks (Plumet et al, 1991;Plumet et al, 1993).…”

Embryonic amygdalar transplants in adult rats with motor cortex lesions: a molecular and electrophysiological analysis

“…Traumatic alterations of the axonal wiring, such as those happening in cortical lesions, immediately produce a permanent functional impairment which leads to behavioral deficits and have severe anatomical consequences (Sorensen et al, 1989; Plumet et al, 1993; Gaillard et al, 1998; Riolobos et al, 2001; Chen et al, 2002). Embryonic tissue transplanted into the damaged cortex of adult rats has shown successful survival and establishment of reciprocal connections between the host and grafted tissue (Castro et al, 1988; Xu et al, 1991; Plumet et al, 1993; Roger and Ebrahimi-Gaillard, 1994; Frappe et al, 1999; Chen et al, 2002; Gaillard et al, 2007; Gaillard and Domballe, 2008; Santos-Torres et al, 2009) and has lead to behavioral graft-dependent recovery (Labbe et al, 1983; Fernandez-Ruiz et al, 1991; Plumet et al, 1991; Riolobos et al, 2001; Heredia et al, 2004). Therefore, certain level of adequate axonal wiring seems to be necessary for the reconstruction of cortical circuitry and restoration of lost brain function.…”