Figure 3. Mechanisms of exogenous stem cell action.

Exogenous stem cells may act via multiple mechanisms to restore function following brain injury. Neuroprotective actions, which could include modulation of inflammation or secretion of neuroprotective compounds, may rescue dysfunctional neurons, thereby preserving existing neural circuitry. Once a host neuron has died, stem cells may conceivably be used to replace the lost neuron, however, effective cell replacement may be dependent upon preservation of surrounding cytoarchitecture. Assuming original circuits cannot be maintained due to retraction of afferent projections after the neuron dies, or due to cavitation of the injury site, stem cells may still participate in the formation of new circuits. This may occur directly via synaptic incorporation into new circuitry, or indirectly by promoting the formation or maintanence of new connections by host neurons. In either case, such generation of new synaptic connections is termed synaptic plasticity. A causal link has not yet been established between functional benefit after cell transplantation following stroke and the synaptic integration of grafted cells. Images adapted from Squire et al (2003).