Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats

Author:

Manni Luigi1,Leotta Eleonora1,Mollica Ilia1,Serafino Annalucia1,Pignataro Annabella12,Salvatori Illari23,Conti Giorgio4,Chiaretti Antonio5,Soligo Marzia1ORCID

Affiliation:

1. Institute of Translational Pharmacology National Research Council of Italy (CNR) Rome Italy

2. IRCCS Fondazione Santa Lucia Rome Italy

3. Department of Experimental Medicine, Faculty of Medicine University of Rome ‘La Sapienza‘ Rome Italy

4. Intensive Pediatric Therapy and Pediatric Trauma Center, Department of Emergency, Anesthesiological and Reanimation Sciences Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy

5. Institute of Pediatrics, Department of Woman and Child Health Fondazione Policlinico Universitario A. Gemelli IRCCS Rome Italy

Abstract

Background and PurposeTraumatic brain injury (TBI) comprises a primary injury directly induced by impact, which progresses into a secondary injury leading to neuroinflammation, reactive astrogliosis, and cognitive and motor damage. To date, treatment of TBI consists solely of palliative therapies that do not prevent and/or limit the outcomes of secondary damage and only stabilize the deficits. The neurotrophin, nerve growth factor (NGF), delivered to the brain parenchyma following intranasal application, could be a useful means of limiting or improving the outcomes of the secondary injury, as suggested by pre‐clinical and clinical data.Experimental ApproachWe evaluated the effect of acute intranasal treatment of young (20‐postnatal day) rats, with NGF in a TBI model (weight drop/close head), aggravated by hypoxic complications. Immediately after the trauma, rats were intranasally treated with human recombinant NGF (50 μg·kg−1), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later.Key ResultsAcute intranasal NGF prevented the onset of TBI‐induced motor disabilities, and decreased reactive astrogliosis, microglial activation and IL‐1β content, which after TBI develops to the same extent in the impact zone and the hypothalamus.Conclusion and ImplicationsIntranasal application of NGF was effective in decreasing the motor dysfunction and neuroinflammation in the brain of young rats in our model of TBI. This work forms an initial pre‐clinical evaluation of the potential of early intranasal NGF treatment in preventing and limiting the disabling outcomes of TBI, a clinical condition that remains one of the unsolved problems of paediatric neurology.

Publisher

Wiley

Subject

Pharmacology

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