The neurogenesis amount in central nervous system (CNS) stimulated by the injury or diseases is so small that neural stem cells (NSCs) cannot specifically differentiate into the ideal phenotypes to repair the injured CNS. The transplanted exogenous NSCs also have such problems as poor survival and insufficient neuronal differentiation. In this study, the behavior of NSCs from the spinal cord of adult rats was compared at the neurosphere level after the respective addition of the brain-derived neurotrophic factor (BDNF) daily, the BDNF-loaded plasma–collagen matrix, the plasma–collagen matrix alone, or the defined medium alone. The results suggested that the BDNF, either in the control release form or in the soluble form, initiated NSCs proliferation and differentiation by activating receptors Trk B and p75NTR. BDNF also increased the differentiation percentage of adult NSCs into neurons and supported the long-term cell survival and growth. The BDNF was stably released by the plasma-collagen matrix for up to 21 days. The plasma–collagen matrix alone showed its biocompatibility with cells by facilitating the adhesion, survival, and differentiation of NSCs. The NSCs in the defined medium alone group showed poor survival and a very low level of neuronal differentiation and proliferation abilities than above three groups. This study suggested that the BDNF-loaded plasma–collagen matrix may provide a promising means to resolve either the poor survival and insufficient neuronal differentiation of transplanted exogenous NSCs, or stimulating the intrinsic NSCs to proliferate and differentiate into neurons so as to repair the injured adult CNS. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.