Transplantation of neural stem cells (NSC) has shown to elicit functional recovery in experimental animal and human models of neural disorders pertaining to cell Loss or degeneration. However, the underlying mechanisms of the regimen are not well understood. The scenarios Lead to the speculation of neuroregeneration and replacement of lost neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). The repair per se is extremely complex involving the re-building and modulation of synapses, neurites, neural cells and glial, cells. Neurotrophins, which nourish the CNS and the PNS, may attribute to the functional improvement after neural stem cell trans plantation. Recent studies suggested the CNS plasticity may be modulated by the class I major histocompatibility complex (MHC), which are in turn regulated by neurotrophins. Based upon these findings, we speculate that the neurotrophins derived from the transplanted NSC may modulate the expression of the major histocompatibility complex in the injured microenvironment to facilitate neurological recovery. The proposition may have clues on the development of novel treatment modality to cure CNS injury. (c) 2006 Elsevier Ltd. All rights reserved.