Almost every mammalian cell and tissue is constantly affected by mechanical signals. Such signals must be recognized and processed to ensure unaffected optimal cell function. One of the most prominent mechanical signals is strain. Although amplitude and frequency of strain varies for different tissues, highly conserved molecular mechanisms transfer the mechanical signal into chemical signal cascades to ultimately induce cellular responses. Most interestingly, such mechanisms are also fully established in neuronal networks although tissues as e.g. the brain are largely protected from mechanical stresses by the skull. Furthermore, we could show that cyclic strain is regulating various further functional aspects in neurons as growth direction of neuronal cells or neuronal branching to ultimately form functional meshworks. Such networks are highly resilient against high amplitudes of strain. We characterize in detail underlying mechanisms for strain signals that induce or support neuronal functionality on single cell and functional meshwork level. Furthermore, we characterize functional neuronal meshworks after intense straining to simulate brain trauma events with subsequent induction of neuronal damage protection on different time scales.