Background and purpose: Traumatic 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 approach: We 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 results: Acute 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 implications: Intranasal 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.

Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats / Manni, Luigi; Leotta, Eleonora; Mollica, Ilia; Serafino, Annalucia; Pignataro, Annabella; Salvatori, Illari; Conti, Giorgio; Chiaretti, Antonio; Soligo, Marzia. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 1476-5381. - 180:15(2023), pp. 1949-1964. [10.1111/bph.16056]

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

Leotta, Eleonora;Mollica, Ilia;Salvatori, Illari;Soligo, Marzia
2023

Abstract

Background and purpose: Traumatic 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 approach: We 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 results: Acute 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 implications: Intranasal 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.
2023
intranasal delivery; microglia; motor dysfunctions; nerve growth factor; paediatric rat; reactive astrogliosis; traumatic brain injury
01 Pubblicazione su rivista::01a Articolo in rivista
Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats / Manni, Luigi; Leotta, Eleonora; Mollica, Ilia; Serafino, Annalucia; Pignataro, Annabella; Salvatori, Illari; Conti, Giorgio; Chiaretti, Antonio; Soligo, Marzia. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 1476-5381. - 180:15(2023), pp. 1949-1964. [10.1111/bph.16056]
File allegati a questo prodotto
File Dimensione Formato  
Manni_Acute_2023.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 11.41 MB
Formato Adobe PDF
11.41 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1695369
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 4
social impact