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

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Brain Injuries, Traumatic*/drug therapy ; Brain Injuries, Traumatic*/metabolism ; Brain Injuries*/drug therapy; Child ; Rats ; Humans ; Animals ; Nerve Growth Factor ; Neuroinflammatory Diseases ; Gliosis ; Inflammation ; Disease Models, Animal

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 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

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Keywords: intranasal delivery; microglia; motor dysfunctions; nerve growth factor; paediatric rat; reactive astrogliosis; traumatic brain injury

9061-61-4 (Nerve Growth Factor)

Date Created: 20230213 Date Completed: 20230707 Latest Revision: 20230718

20240628

10.1111/bph.16056

36780920