Acute intranasal treatment with Nerve Growth Factor limits the onset of traumatic brain injury in young rats

Background and Purpose:Traumatic brain injury (TBI) comprises a primary injurydirectly induced by impact, which progresses into a secondary injury leading toneuroinflammation, reactive astrogliosis, and cognitive and motor damage. To date,treatment of TBI consists solely of palliative therapies that do not prevent and/orlimit the outcomes of secondary damage and only stabilize the deficits. The neurotro-phin, nerve growth factor (NGF), delivered to the brain parenchyma following intra-nasal application, could be a useful means of limiting or improving the outcomes ofthe secondary injury, as suggested by pre-clinical and clinical data.Experimental Approach:We evaluated the effect of acute intranasal treatment ofyoung (20-postnatal day) rats, with NGF in a TBI model (weight drop/close head),aggravated by hypoxic complications. Immediately after the trauma, rats were intra-nasally treated with human recombinant NGF (50?gkg1), and motor behaviouraltest, morphometric and biochemical assays were carried out 24 h later.Key Results:Acute intranasal NGF prevented the onset of TBI-induced motordisabilities, and decreased reactive astrogliosis, microglial activation and IL-1?content, which after TBI develops to the same extent in the impact zone and thehypothalamus.Conclusion and Implications:Intranasal application of NGF was effective in decreas-ing the motor dysfunction and neuroinflammation in the brain of young rats in ourmodel of TBI. This work forms an initial pre-clinical evaluation of the potential of earlyintranasal NGF treatment in preventing and limiting the disabling outcomes of TBI, aclinical condition that remains one of the unsolved problems of paediatric neurology.KEYWORDSintranasal delivery, microglia, motor dysfunctions, nerve growth factor, paediatric rat, reactiveastrogliosis, traumatic brain injury