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

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 μgÁkg À1 ), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later.

Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury

“…Successful translation of IN administration of therapeutic NSCs will be more cost-effective, non-invasive, and safer than current approaches of cellular therapies because it can be done in an outpatient setting and can overcome the risks and bottlenecks associated with intravenous and intracranial administration. Multiple therapies have been shown to be effective after in delivery including proteins, siRNA, reporter genes in preclinical and clinical studies [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] . In our future studies, we will explore the IN administration of LMNSC008 cell using the Impel Neuropharma Precision Olfactory Delivery (POD) device and we will compare POD to the use of a basic drop approach.…”

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome

“…More recently our group demonstrated a promising pharmacological activity of acute intranasal NGF in the prevention of TBI motor dysfunction and neuroinflammation in young rats. These results suggested a potential use as acute treatment immediately after traumatic injuries in order to block the primary and secondary damage of TBI [ 24 ]; d) preliminary clinical data demonstrated that intraventricular and intranasal NGF administration has been safe and effective in improving clinical functions in children with severe long-term neurological sequelae after TBI and meningitis, respectively [ 12 , 25 – 28 ]. Recently, promising results have also been reported by the combined treatment of intranasal human-recombinant NGF (hr-NGF) and transcranial direct current stimulation (tDCS) in 3 children with chronic vegetative state after out-of-hospital cardiac arrest [ 29 ].…”