Transplant and ganglioside GM1 mediated neuronal recovery in rats with brain lesions.

Transplants of fetal brain tissue or injections of ganglioside GM1, given to rats with unilateral, left medial frontal cortex lesions, altered the concentrations of neuronal and glial marker proteins in cortex both adjacent and contralateral to the lesion. The markers were: the neural cell adhesion molecule (NCAM) and D3-protein, both present in neuronal and synaptic membranes; synaptophysin, present in synaptic vesicles; glial fibrillary acidic protein (GFAP) enriched in reactive astrocytes, and the astrocytic glutamine synthetase. After 21 days the concentrations of NCAM, D3 and synaptophysin in brain tissue adjacent to the lesions were decreased by 39, 32 and 42%, respectively, indicating neuronal damage. In the injured rats the GFAP concentration was increased 77%, indicating activation of astrocytes. However, astroglial proliferation was not altered as indicated by the nearly unchanged glutamine synthetase concentrations. The levels of the neuronal markers NCAM, D3 and synaptophysin showed significantly less decline in injured rats treated 7 days after the lesions with transplants or with daily injections of 30 mg/kg GM1. The decrease respectively constituted 23 (NCAM), 31 (D3) and 41% (synaptophysin) in rats with transplants and 23 (NCAM), 16 (D3) and 28% (synaptophysin) in rats treated with GM1. In another group of rats the efficacy of transplants was studied 34 days after lesions. NCAM and D3 in tissue adjacent to the lesions were decreased by 50 and 29%, respectively. In rats which received transplants the decrease was only 27 and 16%, respectively. Moreover, as measured by GFAP concentration, activation of astrocytes was less in rats with transplants (93% increased) compared with rats with lesions only (163%). In contralateral frontal cortex, the effects of lesions were similar but less pronounced. In this brain area also the treatments significantly counteracted the loss of neuronal and glial markers. Previous studies have demonstrated that synaptic remodelling is reflected by the ratios of NCAM to marker proteins for mature synapses. Twenty-one days after the initial injury to the brain the ratios of NCAM to D3 and synaptophysin were significantly increased in frontal cortex ipsilateral to the injury in rats with transplants (26 and 33%, respectively). In contrast, compared with values for injured rats, the calculated ratios were not changed, whereas all neuronal marker proteins were significantly increased in rats treated with GM1. The results suggest that transplants mediate neuronal recovery by inducing dendritic sprouting followed by synaptic remodelling whereas gangliosides mediate recovery by counteracting neuronal degeneration.