Neurotrophins Time Point Intervention after Traumatic Brain Injury: From Zebrafish to Human

Cacialli, Pietro

doi:10.3390/ijms22041585

Cited by 25 publications

(15 citation statements)

References 127 publications

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“…Zebrafish have become a prominent vertebrate model for studying diseases [ 36 , 37 ] since they have 82% orthologues of human disease-associated genes [ 37 ]. Recent evidence affirms that zebrafish represent a novel suitable model to study Alzheimer’s disease [ 38 ], Huntington’s disease [ 39 ], traumatic brain injury [ 32 , 40 ], and sensory organs’ diseases, especially blindness and deafness. Among factors involved in those pathologies is the BDNF/TrkB axis.…”

Section: Introductionmentioning

confidence: 99%

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

Aragona

Porcino

Guerrera

et al. 2022

IJMS

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The brain-derived neurotrophic factor (BDNF) was discovered in the last century, and identified as a member of the neurotrophin family. BDNF shares approximately 50% of its amino acid with other neurotrophins such as NGF, NT-3 and NT-4/5, and its linear amino acid sequences in zebrafish (Danio rerio) and human are 91% identical. BDNF functions can be mediated by two categories of receptors: p75NTR and Trk. Intriguingly, BDNF receptors were highly conserved in the process of evolution, as were the other NTs’ receptors. In this review, we update current knowledge about the distribution and functions of the BDNF-TrkB system in the sensory organs of zebrafish. In fish, particularly in zebrafish, the distribution and functions of BDNF and TrkB in the brain have been widely studied. Both components of the system, associated or segregated, are also present outside the central nervous system, especially in sensory organs including the inner ear, lateral line system, retina, taste buds and olfactory epithelium.

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Section: Introductionmentioning

confidence: 99%

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

Aragona

Porcino

Guerrera

et al. 2022

IJMS

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“…It is important to note that the reasons why some patients experience long-term sequelae in these domains, while others do not, is not well understood and requires further research. Further, there are no drugs currently available to treat TBI [49,50]. However, previous preclinical studies of drugs have shown positive signs when patients diagnosed with mTBI receive drug therapies for more than 12 h. Thus, future clinical trials may want to test the efficacy of drug therapies on functional outcomes such as return to work or recovery [50].…”

Section: Discussionmentioning

confidence: 99%

“…Further, there are no drugs currently available to treat TBI [49,50]. However, previous preclinical studies of drugs have shown positive signs when patients diagnosed with mTBI receive drug therapies for more than 12 h. Thus, future clinical trials may want to test the efficacy of drug therapies on functional outcomes such as return to work or recovery [50].…”

Section: Discussionmentioning

confidence: 99%

Common Symptoms of Mild Traumatic Brain Injury and Work Functioning of Active-Duty Service Members with a History of Deployment

Richard

Patel

Gedeon

et al. 2021

IJERPH

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This study used data from the Military Health System Data Repository to examine the association between mild traumatic brain injuries (mTBI) and work functioning such as work duty limitations, hospital emergency room visits and inpatient admissions for active-duty service members (ADSMs). Further, this study assessed the role that common symptoms of mTBI play in work functioning. Multivariate results showed that having a mTBI diagnosis is not a major factor that results in being “released with work duty limitations”. However, findings from these regression models also showed that the interaction of mTBI with cognitive and linguistic symptoms resulted in odds of 3.63 (CI: 1.40–9.36, p < 0.01) for being “released with work duty limitations” and odds of 4.98 (CI: 1.16–21.39, p < 0.05) for having any emergency department visits compared to those with no diagnosis of mTBI and none of these symptoms. Additionally, the interaction of mTBI with sleep disturbance and chronic pain showed odds of 2.72 (CI: 1.31–5.65, p < 0.01) and odds of 11.56 (CI: 2.65–50.44, p < 0.01) for being “released with work duty limitations” compared to those with no diagnosis of TBI and none of these symptoms, respectively. Further research is needed to investigate the association between mTBI and duration of time off work to provide a comprehensive understanding of the effect of mTBI on work functioning in the Military Health System.

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“…Preclinical and clinical studies have also demonstrated a pharmacological value of NGF in the treatment of neurotrauma outcomes ( Kromer, 1987 ; Cacialli, 2021 ). The rationale behind these studies does not necessarily include the effect of NGF on cholinergic neurons, but extends to other peculiarities of the biological action of NGF.…”

Section: An Extended Rationale For the Use Of Ngf In Diseases Of The Central Nervous Systemmentioning

confidence: 99%

Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

et al. 2021

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Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.

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Neurotrophins Time Point Intervention after Traumatic Brain Injury: From Zebrafish to Human

Cited by 25 publications

References 127 publications

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

Common Symptoms of Mild Traumatic Brain Injury and Work Functioning of Active-Duty Service Members with a History of Deployment

Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

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