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Disruptions in physical substrates of vision following traumatic brain injury
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
The hypothalamus is the other major part of the diencephalon. The hypothalamus has many distinct nuclei. It maintains the body’s internal state, serving as a thermostat to maintain body homeostasis. It houses brain centers for the autonomic nervous system and exerts higher level control of the neuroendocrine system, the latter of which has crosstalk with the neuroimmune system. It contains the suprachiasmatic nucleus, the pacemaker for the circadian cycle, which is entrained by light (nonimage) processed by the nonimaging retinal ganglion cells.
TLR3 activation with poly I:C exacerbates escalated alcohol consumption in dependent male C57BL/6J mice
Published in The American Journal of Drug and Alcohol Abuse, 2023
Anny Gano, Christina L. Lebonville, Howard C. Becker
A surprising observation in Experiment 2 was the lack of a strong behavioral response to stress in the TMT control group during reinstatement testing. Though stress-induced reinstatement was observed in the poly I:C group, the VEH group did not show a reinstatement response to TMT until ethanol became available in the second half of the session. There is no clear explanation for this outcome, as we previously showed TMT to be an effective stressor in inducing ethanol-relapse behavior (39). Although this makes it difficult to discern a true “sensitization” effect for poly I:C challenge in terms of the alcohol-seeking component, mice that received poly I:C consumed more ethanol than the control group when responding yielded access to ethanol. The relationship between stress and the immune system is complex and bidirectional (46–50). It has been shown that stress history can affect the immune response to ethanol (13) and prime the neuroimmune system for an exaggerated response to a subsequent challenge (48,51–54). These works have proposed that stress may create a CNS environment conducive to pro-inflammatory activation by altering the state of microglia. While there is a rich literature discussing the effects of stress on neuroimmune priming of microglia, there is less information on the reverse, i.e., neuroimmune events priming microglia to respond to stress. The data in our Experiment 2 indicate that this pathway may work both ways.
Is chronic pain as an autoimmune disease?
Published in Canadian Journal of Pain, 2022
Sex differences have a biological basis and are undoubtedly complex. Sex-associated steroids cause activation of some pain responses and analgesic efficacy in adults. Perinatal dimorphisms in testosterone levels produce enduring organizational differences in males and females. Various lines of evidence support that immune-triggered conditions exhibit a sex bias in children prior to the onset of puberty,83,84 and therefore it is important to explore facets other than gonadal hormones to understand sex differences in chronic pain. In addition to the action of sex hormones on nociceptive circuits, genes mapping to the X and Y chromosomes are considered to be important players, with the neuroendocrine system modulating the effects stemming from the sex chromosome complement. Hence, research in chronic pain, from a patient perspective, will require fundamentally improving therapeutic interventions to provide precision medicine for feamales and males. It potentially may require the direct manipulation of gonadal hormones in relevant female and male animal models at different life stages. This will be important to determine how hormonal and sex chromosomal influences interact to modulate the neuroimmune system. It will provide a better fundamental understanding of their roles in the development, maturation, and dysregulation of nociceptive circuits.
Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update
Published in Expert Opinion on Pharmacotherapy, 2022
Jonna M. Leyrer-Jackson, Amanda M. Acuña, M. Foster Olive
OUD is a chronic disease prone to relapse that can be, in many cases, ameliorated with pharmacological interventions. While current treatment options are not successful for every individual affected by OUD, there are options available to increase the likelihood of abstinence and decrease the propensity of relapse. Yet, because current treatment options rely heavily on targeting the opioid system as opposed to other contributing mechanistic factors such as the neuroimmune system, treatment options have much room for improvement. Above we have highlighted the use of multiple OUD pharmacotherapies including methadone, tramadol, and buprenorphine and their use as replacement therapies, naltrexone and naloxone and their ability to prevent activation of MORs and promote detoxification, as well as non-FDA-regulated, over-the-counter substances, such as kratom and N-acetylcysteine, which have shown some promising results for reducing opioid craving. We have also highlighted the effectiveness of combining treatments such as buprenorphine and naloxone, which serves as a novel approach for treating OUDs and suggests that further research be conducted on the combination of pharmacotherapies to increase treatment efficacy. Taken together, this review highlights the current treatment strategies for individuals suffering from OUD and provides insight into new treatment strategies that may prove beneficial for improving treatment outcomes in these patients.