Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury.

Carmela Belardo,Rosamaria Cristina Rubino,Gorizio Pieretti,Flavia Ricciardi,Ida Marabese,Rosmara Infantino,Sabatino Maione,Francesca Guida,Livio Luongo,Salvatore Paino,Monica Iannotta,Serena Boccella,Luigi Stella,Rosa Maisto

doi:10.3389/fphar.2019.00352

Carmela Belardo, Rosamaria Cristina Rubino + Show 12 more

Open Access

https://doi.org/10.3389/fphar.2019.00352

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Abstract

Neurological dysfunctions are the most impactful and persistent consequences of traumatic brain injury (TBI). Indeed, previous reports suggest that an association between TBI and chronic pain syndromes, as well anxio-depressive behaviors, tends to be more common in patients with mild forms of TBI. At present, no effective treatment options are available for these symptoms. In the present study, we used a weight drop mild TBI mouse model to investigate the effect of a commercially available 10% Cannabidiol (CBD) oil on both the sensorial and neuropsychiatric dysfunctions associated with mild TBI through behavioral and biomolecular approaches. TBI mice developed chronic pain associated with anxious and aggressive behavior, followed by a late depressive-like behavior and impaired social interaction. Such behaviors were related with specific changes in neurotransmitters release at cortical levels. CBD oral treatment restored the behavioral alterations and partially normalized the cortical biochemical changes. In conclusion, our data show some of the brain modifications probably responsible for the behavioral phenotype associated with TBI and suggest the CBD as a pharmacological tool to improve neurological dysfunctions caused by the trauma.

Highlights

The phytocannabinoid cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, exhibits a broad spectrum of potential therapeutic properties, including neuroprotective effects in Central Nervous System (CNS) disorders (Fernández-Ruiz et al, 2013; De Gregorio et al, 2018; Schonhofen et al, 2018)
We previously showed that mTBI induced late neurological dysfunctions in mice and identified electrophysiological changes at the cortical level possibly associated with symptomatology (Guida et al, 2017a)
It is possible that the rearing activity in our model may reflect a kind of recklessness-like behavior, as previously reported in Traumatic brain injury (TBI) mice (Guida et al, 2017a) and humans (DSM V). mTBI mice presented a typical phenotype, characterized by an aggressive behavior followed by a depressive-like behavior

Summary

Introduction

The phytocannabinoid cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, exhibits a broad spectrum of potential therapeutic properties, including neuroprotective effects in Central Nervous System (CNS) disorders (Fernández-Ruiz et al, 2013; De Gregorio et al, 2018; Schonhofen et al, 2018). Traumatic brain injury (TBI) is a complex injury with a number of symptoms accompanied by inflammatory process and cell death (Arciniegas, 2011; Liu et al, 2019). It is characterized by an initial neuroinflammation, mediated by a rapid glia cells activation, peripheral immune cells recruitment and secretion of inflammatory cytokines, followed by the late appearance of psychologically debilitating symptoms and cognitive impairments (Woodcock and Morganti-Kossmann, 2013). It is assumed that the secondary neuropsychiatric changes that occur as a consequence of trauma are associated with plastic rearrangements at hippocampal and cortical circuitry (Schwarzbold et al, 2008)

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