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Br J Pharmacol ; 180(15): 1949-1964, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36780920

RESUMO

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-1ß 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.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Criança , Ratos , Humanos , Animais , Fator de Crescimento Neural , Doenças Neuroinflamatórias , Gliose , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas/tratamento farmacológico , Inflamação , Modelos Animais de Doenças
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