Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury

Traumatic brain injury is one of the main causes of mortality and disability worldwide. Traumaticbrain injury is characterized by a primary injury directly induced by the impact, which progressesinto a secondary injury that leads to cellular and metabolic damages, starting in the first fewhours and days after primary mechanical injury. To date, traumatic brain injury is not targetableby therapies aimed at preventing and/or limiting the outcomes of secondary damage but only bypalliative therapies. Nerve growth factor is a neurotrophin targeting neuronal and non-neuronalcells, potentially useful in preventing/limiting the outcomes of secondary damage in traumaticbrain injury. This potential has further increased in the last two decades since the possibility ofreaching neurotrophin targets in the brain through its intranasal delivery has been exploited. Indeed,molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrierand reach their therapeutic targets in the brain, with favorable kinetics, dynamics, and safety profile.In the first part of this review, we aimed to report the traumatic brain injury-induced dysfunctionalmechanisms that may benefit from nerve growth factor treatment. In the second part, we thenexposed the experimental evidence relating to the action of nerve growth factor (both in vitro andin vivo, after administration routes other than intranasal) on some of these mechanisms. In the lastpart of the work, we, therefore, discussed the few manuscripts that analyze the effects of treatmentwith nerve growth factor, intranasally delivered to the brain parenchyma, on the outcomes oftraumatic brain injury