scholarly journals Review of the Role of the Brain in Chemotherapy-Induced Peripheral Neuropathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Maryam Omran ◽  
Elizabeth K. Belcher ◽  
Nimish A. Mohile ◽  
Shelli R. Kesler ◽  
Michelle C. Janelsins ◽  
...  

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating, and dose-limiting side effect of many chemotherapy regimens yet has limited treatments due to incomplete knowledge of its pathophysiology. Research on the pathophysiology of CIPN has focused on peripheral nerves because CIPN symptoms are felt in the hands and feet. However, better understanding the role of the brain in CIPN may accelerate understanding, diagnosing, and treating CIPN. The goals of this review are to (1) investigate the role of the brain in CIPN, and (2) use this knowledge to inform future research and treatment of CIPN. We identified 16 papers using brain interventions in animal models of CIPN and five papers using brain imaging in humans or monkeys with CIPN. These studies suggest that CIPN is partly caused by (1) brain hyperactivity, (2) reduced GABAergic inhibition, (3) neuroinflammation, and (4) overactivation of GPCR/MAPK pathways. These four features were observed in several brain regions including the thalamus, periaqueductal gray, anterior cingulate cortex, somatosensory cortex, and insula. We discuss how to leverage this knowledge for future preclinical research, clinical research, and brain-based treatments for CIPN.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joseph Bryant ◽  
Sanketh Andhavarapu ◽  
Christopher Bever ◽  
Poornachander Guda ◽  
Akhil Katuri ◽  
...  

AbstractThe combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB–Akt–NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies.


Author(s):  
Brandon Gunasekera ◽  
Kelly Diederen ◽  
Sagnik Bhattacharyya

Abstract Background Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing. Aims We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine. Methods This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis Results There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC. Conclusions There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.


2011 ◽  
Vol 21 (3) ◽  
pp. 88-95 ◽  
Author(s):  
Deryk S. Beal

We are amassing information about the role of the brain in speech production and the potential neural limitations that coincide with developmental stuttering at a fast rate. As such, it is difficult for many clinician-scientists who are interested in the neural correlates of stuttering to stay informed of the current state of the field. In this paper, I aim to inspire clinician-scientists to tackle hypothesis-driven research that is grounded in neurobiological theory. To this end, I will review the neuroanatomical structures, and their functions, which are implicated in speech production and then describe the relevant differences identified in these structures in people who stutter relative to their fluently speaking peers. I will conclude the paper with suggestions on directions of future research to facilitate the evolution of the field of neuroimaging of stuttering.


2021 ◽  
Author(s):  
Wafa Abdelghaffar ◽  
Oussama Sidhom ◽  
Lilia Laadhar ◽  
Rym Rafrafi

The involvement of immunity in the pathogenesis of schizophrenia and related psychoses was suspected a century ago but was shadowed by the dopaminergic hypothesis after the discovery of antipsychotics. We currently know that this latter theory has many limits and cannot account for the wide variety of psychotic conditions. The immune-inflammatory theory is now one of the most promising axes of research in terms of pathogenesis of several mental health conditions. Immunity and inflammation play a role at least in a subgroup of patients with psychosis. The immune system is complex with a variety of components and mediators that can all have effects on the brain and thus mediate psychiatric symptoms. In this chapter we will explore the scientific evidence of the role of immune system in pathophysiology of psychosis. The sections of this chapter will discuss the role of innate system components (cytokines, microglia, inflammation.), the role of adaptive system (lymphocytes and antibodies) with a section focusing on auto-immunity and particularly antineuronal antibodies. Finally we will discuss how this research can impact patients management and elaborate recommendations for future research.


1987 ◽  
Vol 252 (6) ◽  
pp. H1183-H1191
Author(s):  
C. Iadecola ◽  
P. M. Lacombe ◽  
M. D. Underwood ◽  
T. Ishitsuka ◽  
D. J. Reis

We studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg), paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [14C]iodoantipyrine and alpha-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain (n = 5; P less than 0.01, analysis of variance) and elevated plasma CAs substantially (n = 4). Acute bilateral adrenalectomy abolished the increase in plasma epinephrine (n = 4), reduced the increases in flow (n = 6) in cerebral cortex (P less than 0.05), and abolished them elsewhere in brain (P greater than 0.05). Comparable effects on rCBF were obtained by selective adrenal demedullation (n = 7) or pretreatment with propranolol (1.5 mg/kg iv) (n = 5). DMRF stimulation did not increase the permeability of the BBB to AIB (n = 5). We conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulation allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function.


2014 ◽  
Vol 26 (5) ◽  
pp. 1131-1140 ◽  
Author(s):  
Malia Mason ◽  
Joe C. Magee ◽  
Susan T. Fiske

The negotiation of social order is intimately connected to the capacity to infer and track status relationships. Despite the foundational role of status in social cognition, we know little about how the brain constructs status from social interactions that display it. Although emerging cognitive neuroscience reveals that status judgments depend on the intraparietal sulcus, a brain region that supports the comparison of targets along a quantitative continuum, we present evidence that status judgments do not necessarily reduce to ranking targets along a quantitative continuum. The process of judging status also fits a social interdependence analysis. Consistent with third-party perceivers judging status by inferring whose goals are dictating the terms of the interaction and who is subordinating their desires to whom, status judgments were associated with increased recruitment of medial pFC and STS, brain regions implicated in mental state inference.


2010 ◽  
Vol 31 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Giuseppe Pignataro ◽  
Elga Esposito ◽  
Ornella Cuomo ◽  
Rossana Sirabella ◽  
Francesca Boscia ◽  
...  

It has been recently shown that a short sublethal brain ischemia subsequent to a prolonged harmful ischemic episode may confer ischemic neuroprotection, a phenomenon termed ischemic postconditioning. Na+/Ca2+ exchanger (NCX) isoforms, NCX1, NCX2, and NCX3, are plasma membrane ionic transporters widely distributed in the brain and involved in the control of Na+ and Ca2+ homeostasis and in the progression of stroke damage. The objective of this study was to evaluate the role of these three proteins in the postconditioning-induced neuroprotection. The NCX protein and mRNA expression was evaluated at different time points in the ischemic temporoparietal cortex of rats subjected to tMCAO alone or to tMCAO plus ischemic postconditioning. The results of this study showed that NCX3 protein and ncx3 mRNA were upregulated in those brain regions protected by postconditioning treatment. These changes in NCX3 expression were mediated by the phosphorylated form of the ubiquitously expressed serine/threonine protein kinase p-AKT, as the p-AKT inhibition prevented NCX3 upregulation. The relevant role of NCX3 during postconditioning was further confirmed by results showing that NCX3 silencing, induced by intracerebroventricular infusion of small interfering RNA (siRNA), partially reverted the postconditioning-induced neuroprotection. The results of this study support the idea that the enhancement of NCX3 expression and activity might represent a reasonable strategy to reduce the infarct extension after stroke.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Saheba Nanda ◽  
Krishna Priya ◽  
Tasmia Khan ◽  
Puja Patel ◽  
Heela Azizi ◽  
...  

Brain imaging studies have identified multiple neuronal networks and circuits in the brain with altered functioning in patients with schizophrenia. These include the hippocampo-cerebello-cortical circuit, the prefrontal-thalamic-cerebellar circuit, functional integration in the bilateral caudate nucleus, and the salience network consisting of the insular cortex, parietal anterior cingulate cortex, and striatum, as well as limbic structures. Attributing psychotic symptoms to any of these networks in schizophrenia is confounded by the disruption of these networks in schizophrenic patients. Such attribution can be done with isolated dysfunction in any of these networks with concurrent psychotic symptoms. We present the case of a patient who presents with new-onset hallucinations and a stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). The implication of these findings in isolating psychotic symptoms of the salience network is discussed.


Author(s):  
Shlomit Ritz Finkelstein

This chapter explores and summarizes the current knowledge about the neurophysiological substrata of the utterance of expletives—its brain regions, pathways, and neurotransmitters, and its interaction with hormones. The chapter presents clinical data that have been gathered directly from patients of aphasia, Tourette syndrome, Alzheimer’s disease, and brain injuries—all are disorders often accompanied with expletives. It also discusses the possible relations between swearing and aggression, swearing and pain, and swearing and social inhibition in the population at large. Finally, the chapter examines the clinical data and the data gathered from the population at large within one frame, and proposes two hypotheses that can serve as possible directions for future research about the biological substrata of swearing. No previous knowledge of the brain is assumed.


Religions ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 468 ◽  
Author(s):  
W. R. Klemm

Neurotheology is an emerging academic discipline that examines mind-brain relationships in terms of the inter-relatedness of neuroscience, spirituality, and religion. Neurotheology originated from brain-scan studies that revealed specific correlations between certain religious thoughts and localized activated brain areas known as “God Spots.” This relatively young scholarly discipline lacks clear consensus on its definition, ideology, purpose, or prospects for future research. Of special interest is the consideration of the next steps using brain scans to develop this field of research. This review proposes nine categories of future research that could build on the foundation laid by the prior discoveries of God Spots. Specifically, this analysis identifies some sparsely addressed issues that could be usefully explored with new kinds of brain-scan studies: neural network operations, the cognitive neuroscience of prayer, biology of belief, measures of religiosity, role of the self, learning and memory, religious and secular cognitive commonalities, static and functional anatomy, and recruitment of neural processing circuitry. God Spot research is poised to move beyond observation to robust hypothesis generation and testing.


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