The trigemino-cardiac reflex (TCR) is defined as a sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea or gastric hypermotility during the stimulation of any of the sensory branches of the trigeminal nerve. The sensory nerve endings of the trigeminal nerve transmit neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. Through this physiological response, adjustments of the systemic and cerebral circulations are initiated to change cerebral blood flow in a manner that is not yet understood. It appears that the cerebrovascular response to hypoxemia is, to a large extent, due to this reflex and generated by the activation of neurons of the rostral ventrolateral reticular nucleus. TCR is therefore an “oxygen-conserving-reflex” in human as it produces cross-tolerance to oxygen deprivation, thus reinforcing cerebral adaptation to oxygen demand/ supply mismatching via energy-sparing pathways. The existence of such endogenous neuroprotective strategies may extend beyond the actually known clinical appearance of the TCR and include the prevention of other potential brain injury states as well. Thus, we show that the beneficial effects of TCR extend beyond providing neuroprotection during the acute phase after ischemia. Induction of growth factor expression and neurogenesis by TCR might be a positive adaptation for an efficient repair and plasticity in the event of an ischemic insult.