International Review Of Neurobiology[JOURNAL]
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200 papers
Substitution therapy for patients with alcohol dependence: Mechanisms of action and efficacy.
Guiraud J, Spanagel R, van den Brink W
Int Rev Neurobiol · 2024 · PMID 38555116 · Publisher ↗
New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, the...
New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD. Here, we explain the mechanistic foundations of alcohol substitution maintenance therapy. Alcohol has many primary targets in the brain (and other organs) and the physical interaction of ethanol molecules with these specific ethanol-sensitive sites on a variety of ionotropic receptors (e.g. GABA-A, NMDA, and nicotinic acetylcholine (nACh) receptors) and ion channels provides the rationale for substitution. As such, a variety of compounds can interact with those ethanol-sensitive sites and can thus substitute for some of the effects of alcohol. For some of these compounds, alcohol discrimination studies have shown their substitution potential. Accordingly, potential substitution treatments include agonists acting at GABA receptors such as sodium oxybate, baclofen and benzodiazepines, NMDA receptor antagonists such as ketamine and memantine, or nAChRs agonists such as varenicline. All these compounds are already approved for other indications and we present clinical evidence for these drugs in the treatment of alcohol withdrawal syndrome (AWS) and in the long-term treatment of AD, and outline future steps for their acceptance as substitution treatment in AD. Finally, we discuss the substitution approach of managed alcohol programs for the most severely affected homeless populations. Results showed that sodium oxybate is probably the closest to a substitution therapy for AD and is already approved for the treatment of AWS and in the long-term treatment of AD in some countries. In conclusion, we argue that better AD treatment can be provided if substitution maintenance treatments for alcohol are implemented at a similar scale as for opioid and nicotine use disorder.
Repurposing drugs for treatment of alcohol use disorder.
Aubin HJ
Int Rev Neurobiol · 2024 · PMID 38555115 · Publisher ↗
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach...
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Current treatments of alcohol use disorder.
Dionisi T, Di Sario G, De Mori L … +10 more , Spagnolo G, Antonelli M, Tarli C, Sestito L, Mancarella FA, Ferrarese D, Mirijello A, Vassallo GA, Gasbarrini A, Addolorato G
Int Rev Neurobiol · 2024 · PMID 38555114 · Publisher ↗
Emerging treatments for alcohol dependence reveal an intricate interplay of neurobiological, psychological, and circumstantial factors that contribute to Alcohol Use Disorder (AUD). The approved strategies balancing thes...
Emerging treatments for alcohol dependence reveal an intricate interplay of neurobiological, psychological, and circumstantial factors that contribute to Alcohol Use Disorder (AUD). The approved strategies balancing these factors involve extensive manipulations of neurotransmitter systems such as GABA, Glutamate, Dopamine, Serotonin, and Acetylcholine. Innovative developments are engaging mechanisms such as GABA reuptake inhibition and allosteric modulation. Closer scrutiny is placed on the role of Glutamate in chronic alcohol consumption, with treatments like NMDA receptor antagonists and antiglutamatergic medications showing significant promise. Complementing these neurobiological approaches is the progressive shift towards Personalized Medicine. This strategy emphasizes unique genetic, epigenetic and physiological factors, employing pharmacogenomic principles to optimize treatment response. Concurrently, psychological therapies have become an integral part of the treatment landscape, tackling the cognitive-behavioral dimension of addiction. In instances of AUD comorbidity with other psychiatric disorders, Personalized Medicine becomes pivotal, ensuring treatment and prognosis are closely defined by individual characteristics, as exemplified by Lesch Typology models. Given the high global prevalence and wide distribution of AUD, a persistent necessity exists for development and improvement of treatments. Current research efforts are steadily paving paths towards more sophisticated, effective typology-based treatments: a testament to the recognized imperative for enhanced treatment strategies. The potential encapsulated within the ongoing research suggests a promising future where the clinical relevance of current strategies is not just maintained but significantly improved to effectively counter alcohol dependence.
AUD in perspective.
de Bejczy A, Addolorato G, Aubin HJ … +5 more , Guiraud J, Korpi ER, John Nutt D, Witkiewitz K, Söderpalm B
Int Rev Neurobiol · 2024 · PMID 38555113 · Publisher ↗
Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol...
Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol in a vast number of diseases, the need for additional interventions and the development of new medicines is considered a priority by the World Health Organization (WHO). As of today, AUD is severely under-treated with a treatment gap nearing 90%, strikingly higher than that for other psychiatric disorders. Patients often seek treatment late in the progress of the disease and even among those who seek treatment only a minority receive medication, mirroring the still-prevailing stigma of the disease, and a lack of access to effective treatments, as well as a reluctance to total abstinence. To increase adherence, treatment goals should focus not only on maintaining abstinence, but also on harm reduction and psychosocial functioning. A personalised approach to AUD treatment, with a holistic view, and tailored therapy has the potential to improve AUD treatment outcomes by targeting the heterogeneity in genetics and pathophysiology, as well as reason for, and reaction to drinking. Also, the psychiatric co-morbidity rates are high in AUD and dual diagnosis can worsen symptoms and influence treatment response and should be considered in the treatment strategies.
Insight gained from using animal models to study pain in Parkinson's disease.
Buhidma Y, Lama J, Duty S
Int Rev Neurobiol · 2024 · PMID 38341233 · Publisher ↗
Pain is one of the key non-motor symptoms experienced by a large proportion of people living with Parkinson's disease (PD), yet the mechanisms behind this pain remain elusive and as such its treatment remains suboptimal....
Pain is one of the key non-motor symptoms experienced by a large proportion of people living with Parkinson's disease (PD), yet the mechanisms behind this pain remain elusive and as such its treatment remains suboptimal. It is hoped that through the study of animal models of PD, we can start to unravel some of the contributory mechanisms, and perhaps identify models that prove useful as test beds for assessing the efficacy of potential new analgesics. However, just how far along this journey are we right now? Is it even possible to model pain in PD in animal models of the disease? And have we gathered any insight into pain mechanisms from the use of animal models of PD so far? In this chapter we intend to address these questions and in particular highlight the findings generated by others, and our own group, following studies in a range of rodent models of PD.
A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms.
Batzu L, Podlewska A, Gibson L … +2 more , Chaudhuri KR, Aarsland D
Int Rev Neurobiol · 2024 · PMID 38341232 · Publisher ↗
The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, dep...
The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, depression, anxiety, and apathy. Due to their high prevalence in people with PD (PwP) and their occurrence in every stage of the disease, from the prodromal to the advanced stage, it is not surprising that PD can be conceptualised as a complex neuropsychiatric disorder. Despite progress in understanding the pathophysiological mechanisms underlying the neuropsychiatric signs and symptoms in PD, and better identification and diagnosis of these symptoms, effective treatments are still a major unmet need. The impact of these symptoms on the quality of life of PwP and caregivers, as well as their contribution to the overall non-motor symptom burden can be greater than that of motor symptoms and require a personalised, holistic approach. In this chapter, we provide a general clinical overview of the major neuropsychiatric symptoms of PD.
Executive dysfunction and cognitive decline, a non-motor symptom of Parkinson's disease captured in animal models.
Iravani MM, Shoaib M
Int Rev Neurobiol · 2024 · PMID 38341231 · Publisher ↗
The non-motor symptoms of Parkinson's disease (PD) have gained increasing attention in recent years due to their significant impact on patients' quality of life. Among these non-motor symptoms, cognitive dysfunction has...
The non-motor symptoms of Parkinson's disease (PD) have gained increasing attention in recent years due to their significant impact on patients' quality of life. Among these non-motor symptoms, cognitive dysfunction has emerged as an area of particular interest where the clinical aspects are covered in Chapter 2 of this volume. This chapter explores the rationale for investigating the underlying neurobiology of cognitive dysfunction by utilising translational animal models of PD, from rodents to non-human primates. The objective of this chapter is to review the various animal models of cognition that have explored the dysfunction in animal models of Parkinson's disease. Some of the more advanced pharmacological studies aimed at restoring these cognitive deficits are reviewed, although this chapter highlights the lack of systematic approaches in dealing with this non-motor symptom at the pre-clinical stages.
Review: Lower urinary tract dysfunction in animal models of Parkinson's disease (PD): Translational aspects for the treatment of PD patients with overactive bladder.
Kitta T, Ogawa T, Kuno S … +2 more , Kakizaki H, Yoshimura N
Int Rev Neurobiol · 2024 · PMID 38341230 · Publisher ↗
Although the loss of dopaminergic neurons in the substantia nigra and consequent motor symptoms are the hallmarks of Parkinson's disease (PD), several non-motor symptoms may appear prior to these typical motor symptoms....
Although the loss of dopaminergic neurons in the substantia nigra and consequent motor symptoms are the hallmarks of Parkinson's disease (PD), several non-motor symptoms may appear prior to these typical motor symptoms. While a variety of non-motor symptoms have emerged as the primary predictor of PD patients' quality of life, even though motor symptoms are undoubtedly distressing. According to a study, the prevalence of lower urinary tract symptoms (LUTS) varies between 27% and 64%, suggesting that PD-related lower urinary tract dysfunction may be affected by the disease stage, the presence of concomitant conditions affecting the lower urinary tract, and other autonomic dysfunctions. Animal models can serve as a platform for research into the causes of PD-related dysfunction and the evaluation of cutting-edge therapeutic approaches although the majority of animal research have been directed toward motor symptoms of PD. At present, the cause of lower urinary tract dysfunction in PD has not been fully clarified although the increasing evidence showing the multiple mechanisms underlying PD-related LUTS has emerged. In this chapter we summarize the findings of basic research in the studies of the lower urinary tract dysfunction using with different animal PD models and we try to shed light on the translational aspects for the development of future treatment modalities in PD patients with LUTS.
Macro and micro-sleep dysfunctions as translational biomarkers for Parkinson's disease.
Lima MMS, Targa ADS, Dos Santos Lima GZ … +2 more , Cavarsan CF, Torterolo P
Int Rev Neurobiol · 2024 · PMID 38341229 · Publisher ↗
Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the...
Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the links between sleep dysfunctions in PD, focusing most closely on those data from animal and mathematical/computational models, as well as in human-based studies that explore the electrophysiological and molecular mechanisms by which PD and sleep may be intertwined, whether as predictors or consequences of the disease. It is possible to clearly state that leucine-rich repeat kinase 2 gene (LRRK2) is significantly related to alterations in sleep architecture, particularly affecting rapid eye movement (REM) sleep and non-REM sleep, thus impacting sleep quality. Also, decreases in gamma power, observed after dopaminergic lesions, correlates negatively with the degree of injury, which brings other levels of understanding the impacts of the disease. Besides, abnormal synchronized oscillations among basal ganglia nuclei can be detrimental for information processing considering both motor and sleep-related processes. Altogether, despite clear advances in the field, it is still difficult to definitely establish a comprehensive understanding of causality among all the sleep dysfunctions with the disease itself. Although, certainly, the search for biomarkers is helping in shortening this road towards a better and faster diagnosis, as well as looking for more efficient treatments.
Investigating affective neuropsychiatric symptoms in rodent models of Parkinson's disease.
Boi L, Fisone G
Int Rev Neurobiol · 2024 · PMID 38341228 · Publisher ↗
Affective neuropsychiatric disorders such as depression, anxiety and apathy are among the most frequent non-motor symptoms observed in people with Parkinson's disease (PD). These conditions often emerge during the prodro...
Affective neuropsychiatric disorders such as depression, anxiety and apathy are among the most frequent non-motor symptoms observed in people with Parkinson's disease (PD). These conditions often emerge during the prodromal phase of the disease and are generally considered to result from neurodegenerative processes in meso-corticolimbic structures, occurring in parallel to the loss of nigrostriatal dopaminergic neurons. Depression, anxiety, and apathy are often treated with conventional medications, including selective serotonin reuptake inhibitors, tricyclic antidepressants, and dopaminergic agonists. The ability of these pharmacological interventions to consistently counteract such neuropsychiatric symptoms in PD is still relatively limited and the development of reliable experimental models represents an important tool to identify more effective treatments. This chapter provides information on rodent models of PD utilized to study these affective neuropsychiatric symptoms. Neurotoxin-based and genetic models are discussed, together with the main behavioral tests utilized to identify depression- and anxiety-like behaviors, anhedonia, and apathy. The ability of various therapeutic approaches to counteract the symptoms observed in the various models is also reviewed.
Setting the clinical context to non-motor symptoms reflected by Park-pain, Park-sleep, and Park-autonomic subtypes of Parkinson's disease.
Qamar MA, Tall P, van Wamelen D … +7 more , Wan YM, Rukavina K, Fieldwalker A, Matthew D, Leta V, Bannister K, Chaudhuri KR
Int Rev Neurobiol · 2024 · PMID 38341227 · Publisher ↗
Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical picture...
Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical pictures and NMS subtypes have recently been proposed, initially based on clinical observations, and later confirmed in data driven analyses of large datasets and in biomarker-based studies. In this chapter, we provide an update on what is known about three common subtypes of NMS in PD. The pain (Park-pain), sleep dysfunction (Park-sleep), and autonomic dysfunction (Park-autonomic), providing an overview of their individual classification, clinical manifestation, pathophysiology, diagnosis, and potential treatments.
Involvement of brain metabolism in neurodevelopmental disorders.
Kotchetkov P, Blakeley N, Lacoste B
Int Rev Neurobiol · 2023 · PMID 37993180 · Publisher ↗
Neurodevelopmental disorders (NDDs) affect a significant portion of the global population and have a substantial social and economic impact worldwide. Most NDDs manifest in early childhood and are characterized by defici...
Neurodevelopmental disorders (NDDs) affect a significant portion of the global population and have a substantial social and economic impact worldwide. Most NDDs manifest in early childhood and are characterized by deficits in cognition, communication, social interaction and motor control. Due to a limited understanding of the etiology of NDDs, current treatment options primarily focus on symptom management rather than on curative solutions. Moreover, research on NDDs is problematic due to its reliance on a neurocentric approach. However, recent studies are broadening the scope of research on NDDs, to include dysregulations within a diverse network of brain cell types, including vascular and glial cells. This review aims to summarize studies from the past few decades on potential new contributions to the etiology of NDDs, with a special focus on metabolic signatures of various brain cells. In particular, we aim to convey how the metabolic functions are intimately linked to the onset and/or progression of common NDDs such as autism spectrum disorders, fragile X syndrome, Rett syndrome and Down syndrome.
A review of the use of psychotropic medication to address challenging behaviour in neurodevelopmental disorders.
Valdovinos MG, Epperson C, Johnson C
Int Rev Neurobiol · 2023 · PMID 37993179 · Publisher ↗
Engagement in challenging behaviour (e.g., aggression, self-injury) is reported to occur in neurodevelopmental disorders such as intellectual disabilities (ID), autism spectrum disorder (ASD), and fragile X syndrome (FXS...
Engagement in challenging behaviour (e.g., aggression, self-injury) is reported to occur in neurodevelopmental disorders such as intellectual disabilities (ID), autism spectrum disorder (ASD), and fragile X syndrome (FXS). Common interventions to address these behaviours include both behavioural and pharmacological approaches. Although psychotropic medications are commonly used to address challenging behaviour in ID, ASD, and FXS, demonstration of the effectiveness of treatment is limited. Furthermore, research examining interaction effects between psychotropic medication, challenging behaviour, and environmental events within specific neurodevelopmental disorders such as ID, ASD, and FXS is scarce. The purpose of this chapter is to provide an overview of challenging behaviour within ID, ASD, and FXS and of the effectiveness of psychotropic medication as an intervention for challenging behaviour within these neurodevelopmental disorders. Finally, research examining how psychotropic medication may impact the relationship between challenging behaviour and environmental events is reviewed.
Glial-mediated dysregulation of neurodevelopment in Fragile X Syndrome.
Napier M, Reynolds K, Scott AL
Int Rev Neurobiol · 2023 · PMID 37993178 · Publisher ↗
Astrocytes are highly involved in a multitude of developmental processes that are known to be dysregulated in Fragile X Syndrome. Here, we examine these processes individually and review the roles astrocytes play in cont...
Astrocytes are highly involved in a multitude of developmental processes that are known to be dysregulated in Fragile X Syndrome. Here, we examine these processes individually and review the roles astrocytes play in contributing to the pathology of this syndrome. As a growing area of interest in the field, new and exciting insight is continually emerging. Understanding these glial-mediated roles is imperative for elucidating the underlying molecular mechanisms at play, not only in Fragile X Syndrome, but also other ASD-related disorders. Understanding these roles will be central to the future development of effective, clinically-relevant treatments of these disorders.
How dendritic spines shape is determined by MMP-9 activity in FXS.
Dziembowska M
Int Rev Neurobiol · 2023 · PMID 37993177 · Publisher ↗
Matrix metalloproteinase-9 (MMP-9) belongs to the family of endopeptidases expressed in neurons and secreted at the synapse in response to neuronal activity. It regulates the pericellular environment by cleaving its prot...
Matrix metalloproteinase-9 (MMP-9) belongs to the family of endopeptidases expressed in neurons and secreted at the synapse in response to neuronal activity. It regulates the pericellular environment by cleaving its protein components. MMP9 is involved in activity-dependent reorganization of spine architecture. In the mouse model of fragile X syndrome (FXS), the most common inherited intellectual disability and the most common single-gene cause of autism, increased synaptic expression of MMP-9 is responsible for the observed dendritic spine abnormalities. In this chapter, I summarize the current data on the molecular regulatory pathways responsible for synaptic MMP-9 expression and discuss the fact that MMP-9 is extracellularly localized, making it a particularly attractive potential target for therapeutic pharmacological intervention in FXS.
Toward an understanding of the role of the exposome on fragile X phenotypes.
Westmark CJ
Int Rev Neurobiol · 2023 · PMID 37993176 · Publisher ↗
Fragile X syndrome (FXS) is the leading known monogenetic cause of autism with an estimated 21-50% of FXS individuals meeting autism diagnostic criteria. A critical gap in medical care for persons with autism is an under...
Fragile X syndrome (FXS) is the leading known monogenetic cause of autism with an estimated 21-50% of FXS individuals meeting autism diagnostic criteria. A critical gap in medical care for persons with autism is an understanding of how environmental exposures and gene-environment interactions affect disease outcomes. Our research indicates more severe neurological and metabolic outcomes (seizures, autism, increased body weight) in mouse and human models of autism spectrum disorders (ASD) as a function of diet. Thus, early-life exposure to chemicals in the diet could cause or exacerbate disease outcomes. Herein, we review the effects of potential dietary toxins, i.e., soy phytoestrogens, glyphosate, and polychlorinated biphenyls (PCB) in FXS and other autism models. The rationale is that potentially toxic chemicals in the diet, particularly infant formula, could contribute to the development and/or severity of ASD and that further study in this area has potential to improve ASD outcomes through dietary modification.
Cholesterol alterations in fragile X syndrome, autism spectrum disorders and other neurodevelopmental disorders.
Benachenhou S, Laroui A, Dionne O … +3 more , Rojas D, Toupin A, Çaku A
Int Rev Neurobiol · 2023 · PMID 37993175 · Publisher ↗
Neurodevelopmental disorders (NDDs) are a group of etiologically diverse diseases primarily associated with abnormal brain development, impaired cognition, and various behavioral problems. The majority of NDDs present a...
Neurodevelopmental disorders (NDDs) are a group of etiologically diverse diseases primarily associated with abnormal brain development, impaired cognition, and various behavioral problems. The majority of NDDs present a wide range of clinical phenotypes while sharing distinct cellular and biochemical alterations. Low plasma cholesterol levels have been reported in a subset of NNDs including, autism spectrum disorder (ASD) and fragile X syndrome (FXS). The present review focuses on cholesterol metabolism and discusses the current evidence of lipid disruption in ASD, FXS, and other genetically related NDDs. The characterization of these common deficits might provide valuable insights into their underlying physiopathology and help identify potential therapeutic targets.
The dopamine hypothesis of autism spectrum disorder: A comprehensive analysis of the evidence.
Pavăl D
Int Rev Neurobiol · 2023 · PMID 37993174 · Publisher ↗
Despite intensive research into the etiopathogenesis of autism spectrum disorder (ASD), limited progress has been achieved so far. Among the plethora of models seeking to clarify how ASD arises, a coherent dopaminergic m...
Despite intensive research into the etiopathogenesis of autism spectrum disorder (ASD), limited progress has been achieved so far. Among the plethora of models seeking to clarify how ASD arises, a coherent dopaminergic model was lacking until recently. In 2017, we provided a theoretical framework that we designated "the dopamine hypothesis of ASD". In the meantime, numerous studies yielded empirical evidence for this model. 4 years later, we provided a second version encompassing a refined and reconceptualized framework that accounted for these novel findings. In this chapter, we will review the evidence backing the previous versions of our model and add the most recent developments to the picture. Along these lines, we intend to lay out a comprehensive analysis of the supporting evidence for the dopamine hypothesis of ASD.
Neuromodulation and quality of life for patient with spasticity after spinal cord injury.
Biktimirov A, Bryukhovetskiy I, Sharma A … +1 more , Sharma HS
Int Rev Neurobiol · 2023 · PMID 37833019 · Publisher ↗
RATIONALE: Spasticity develops in 80% of spinal cord injury cases and negatively affects the patents' quality of life. The most common method of surgical treatment for severe spasticity is a long-term intrathecal baclofe...
RATIONALE: Spasticity develops in 80% of spinal cord injury cases and negatively affects the patents' quality of life. The most common method of surgical treatment for severe spasticity is a long-term intrathecal baclofen therapy (ITB). Long-term spinal cord stimulation is another possible treatment technique. This paper aims to evaluate the changes in quality of life for patients with spasticity who have been treated with neuromodulation (SCS or ITB) in 12 months after the surgery, as well to compare the changes in quality of life for patients who have been treated with spinal cord stimulation and those who received long-term intrathecal baclofen therapy. MATERIALS AND METHODS: The influence of spasticity, experienced by the patients with a spinal cord injury, on their quality of life was analyzed before the surgery and 12 months after it. The severity of the spinal cord damage was determined with the scale of the American Spinal Injury Association (ASIA); spasticity was evaluated with the modified Ashworth scale, Penn Spasm Frequency Scale; pain levels were determined with visual analogue scale (VAS), anxiety and depression levels - with HADS. Functional activity of the patients was evaluated with the help of the Functional Independence Measure (FIM). RESULTS: The treatment results for 33 patients (25 men and 8 women), aged from 18 to 62, are presented. After the trial stimulation, the patients were randomly assigned to either SCS or ITB group (18 and 15 people respectively). The decrease of spasticity in both experimental groups caused lower levels of pain, less functional dependency on other people, lower stress and depression rates and, as a consequence, better quality of life and social adaptation. The obtained results for SCS and ITB groups are statistically similar.
Nanodelivery of histamine H3 receptor inverse agonist BF-2649 with H3 receptor antagonist and H4 receptor agonist clobenpropit induced neuroprotection is potentiated by antioxidant compound H-290/51 in spinal cord injury.
Buzoianu AD, Sharma A, Muresanu DF … +9 more , Feng L, Huang H, Chen L, Tian ZR, Nozari A, Lafuente JV, Sjöqvist PO, Wiklund L, Sharma HS
Int Rev Neurobiol · 2023 · PMID 37833018 · Publisher ↗
Military personnel are often victims of spinal cord injury resulting in lifetime disability and decrease in quality of life. However, no suitable therapeutic measures are still available to restore functional disability...
Military personnel are often victims of spinal cord injury resulting in lifetime disability and decrease in quality of life. However, no suitable therapeutic measures are still available to restore functional disability or arresting the pathophysiological progression of disease in victims for leading a better quality of life. Thus, further research in spinal cord injury using novel strategies or combination of available neuroprotective drugs is urgently needed for superior neuroprotection. In this regard, our laboratory is engaged in developing TiO nanowired delivery of drugs, antibodies and enzymes in combination to attenuate spinal cord injury induced pathophysiology and functional disability in experimental rodent model. Previous observations show that histamine antagonists or antioxidant compounds when given alone in spinal cord injury are able to induce neuroprotection for short periods after trauma. In this investigation we used a combination of histaminergic drugs with antioxidant compound H-290/51 using their nanowired delivery for neuroprotection in spinal cord injury of longer duration. Our observations show that a combination of H3 receptor inverse agonist BF-2549 with H3 receptor antagonist and H4 receptor agonist clobenpropit induced neuroprotection is potentiated by antioxidant compound H-290/51 in spinal cord injury. These observations suggests that histamine receptors are involved in the pathophysiology of spinal cord injury and induce superior neuroprotection in combination with an inhibitor of lipid peroxidation H-290/51, not reported earlier. The possible mechanisms and significance of our findings in relation to future clinical approaches in spinal cord injury is discussed.
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