Use of nanoparticulate drug delivery system for an effective therapeutic outcome against diseases gains immense hope in the study of drug delivery to partially hepatectomised rats. In the present study, partially hepatectomised rats treated with Gamma aminobutyric acid (GABA) and serotonin (5-HT) chitosan nanoparticles, individually and in combination, were evaluated to analyse their role in GABAB, and 5-HT2A receptors functional regulation, interrelated neuronal survival mechanisms by nuclear factor kappa B (NF-kappaB), tumour necrosis factor-a (TNF-alpha), Akt-1 and the antioxidant enzyme superoxide dismutase (SOD) in the cerebral cortex. A significant decrease in GABA, and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the cerebral cortex to trigger the sympathetic innervations during elevated DNA synthesis in the liver. GABAB, and 5-HT2A signalling directly influenced the cyclic AMP response element binding protein (CREB) expression, neuronal survival and ROS mediated cell damage which was confirmed from the gene expression of NF-kappaB, TNF-alpha, Akt-1 and SOD. In addition to enhanced hepatocyte proliferation, GABA and 5-HT chitosan nanoparticle treatment protected the neurons from ROS mediated cell damage and promoted their survival in the cerebral cortex. This has application in liver based diseases and treatments with nanosized active compounds.