Mental disorders (MDs) are highly prevalent and potentially debilitating complex disorders which causes remain elusive. Looking into deeper aspects of etiology or pathophysiology underlying these diseases would be highly beneficial, as the scarce knowledge in mechanistic and molecular pathways certainly represents an important limitation. Association between MDs and inflammation/neuroinflammation has been widely discussed and accepted by many, as high levels of pro-inflammatory cytokines were reported in patients with several MDs, such as schizophrenia (SCZ), bipolar disorder (BD) and major depression disorder (MDD), among others. Correlation of pro-inflammatory markers with symptoms intensity was also reported. However, the mechanisms underlying the inflammatory dysfunctions observed in MDs are not fully understood yet. In this context, microglial dysfunction has recently emerged as a possible pivotal player, as during the neuroinflammatory response, microglia can be over-activated, and excessive production of pro-inflammatory cytokines, which can modify the kynurenine and glutamate signaling, is reported. Moreover, microglial activation also results in increased astrocyte activity and consequent glutamate release, which are both toxic to the Central Nervous System (CNS). Also, as a result of increased microglial activation in MDs, products of the kynurenine pathway were shown to be changed, influencing then the dopaminergic, serotonergic, and glutamatergic signaling pathways. Therefore, in the present review, we aim to discuss how neuroinflammation impacts on glutamate and kynurenine signaling pathways, and how they can consequently influence the monoaminergic signaling. The consequent association with MDs main symptoms is also discussed. As such, this work aims to contribute to the field by providing insights into these alternative pathways and by shedding light on potential targets that could improve the strategies for pharmacological intervention and/or treatment protocols to combat the main pharmacologically unmatched symptoms of MDs, as the SCZ.

In recent years scientific research has established that the nervous and immune systems have shared molecular signaling components. Proteins native to immune cells, which are also found in the brain, have neuronal functions in the nervous system where they affect synaptic plasticity, axonal regeneration, neurogenesis, and neurotransmission. Certain native immune molecules like major histocompatibility complex I (MHC-I), paired immunoglobulin receptor B (PirB), toll-like receptor (TLR), cluster of differentiation-3 zeta (CD3ζ), CD4 co-receptor, and T-cell receptor beta (TCR-β) expression in neurons have been extensively documented. In this review, we provide our opinion and discussed the possible roles of T-cell receptor beta subunits in modulating the function of neurons in the central nervous system. Based on the previous findings of Syken and Shatz., 2003; Nishiyori et al., 2004; Rodriguez et., 1993 and Komal et., 2014; we discuss whether restrictive expression of TCR-β subunits in selected brain regions could be involved in the pathology of neurological disorders and whether their aberrant enhancement in expression may be considered as a suitable biomarker for aging or neurodegenerative diseases like Huntington\'s disease (HD).

Alcohol withdrawal syndrome (AWS) is a common condition that is seen in treatment-seeking patients with Alcohol use disorder (AUD) and alcoholic liver disease (ALD). AWS, which typically starts within 4-6 h of the last alcohol use, can range from mild symptoms such as insomnia, tremors, and autonomic hyperactivity to more severe symptoms such as seizures and delirium tremens. Clinical Institute Withdrawal Assessment Scale-Alcohol Revised (CIWA-Ar) is the most commonly used scale to assess AWS in clinical practice. The presence of moderate withdrawal as indicated by a score of more than 8 is an indication for pharmacotherapy. Lorazepam and oxazepam are preferred agents for the management of AWS in the setting of ALD. In severe ALD, benzodiazepines should be used cautiously with monitoring due to the risk of excessive sedation or precipitating hepatic encephalopathy.

Alcohol use disorder (AUD) is a common condition that develops on the background of heavy alcohol use and is characterised by the loss of control over alcohol use and a compulsion to use alcohol, often despite negative consequences. AUD is a leading cause for the resumption of alcohol use in patients with alcoholic liver disease (ALD) after treatment. Hence it is essential to screen all patients with ALD for the presence of AUD. Screening tools such as alcohol use disorders identification test (AUDIT) and AUDIT-C are used, following which the diagnosis and severity of AUD are determined using DSM-5 criteria. The management of AUD in patients with ALD is best carried out using an integrated approach involving psychiatrists and gastroenterologists/hepatologists. The treatment most often involves a combination of pharmacotherapy and psychosocial interventions which try to achieve and maintain abstinence. Although, there is limited evidence, Baclofen is the first line pharmacological agent for long-term management of AUD in patients with ALD. Intensive psychological interventions such as motivation enhancement therapy and cognitive behavioural therapy are also seen to be beneficial. Treatment retention and follow-up are vital and can positively influence outcomes.

UNASSIGNED: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice.
UNASSIGNED: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and pole-climbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i.
UNASSIGNED: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells.
UNASSIGNED: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presents with the features of herpes simplex encephalitis (HSE), which is rare and has been described in only a few case reports. Our case describes a 17-year-old female with no significant previous medical history presenting with an acute onset of fever, headache, and epilepsy, similar to HSE. Computed tomography of the brain showed bilateral basal ganglia calcification. Magnetic resonance imaging demonstrated gyriform restricted diffusion with T2-weighted images prolongation. Further investigation showed elevated blood lactate concentration at rest. Hence, MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. The clinical presentation and imaging studies of MELAS are variable and may mimic those of HSE. Infection may have also precipitated MELAS manifestation in this patient. Laboratory features, such as elevated lactate, basal ganglia calcification, and gyriform restricted diffusion may be helpful in identifying patients with MELAS.

Glutamate receptors have a key role in the neurobiology of opioid addiction. Using electron microscopic immunocytochemical methods, this project elucidates how sex and chronic immobilization stress (CIS) impact the redistribution of GluN1 and GluA1 within rat hippocampal CA3 pyramidal cells following oxycodone (Oxy) conditioned place preference (CPP). Four groups of female and male Sprague-Dawley rats subjected to CPP were used: Saline- (Sal) and Oxy-injected (3 mg/kg, I.P.) naïve rats; and Sal- and Oxy-injected CIS rats. GluN1: In both naive and CIS rats, Sal-females compared to Sal-males had elevated cytoplasmic and total dendritic GluN1. Following Oxy CPP, near plasmalemmal, cytoplasmic, and total GluN1 decreased in CA3 dendrites of unstressed females suggesting reduced pools of GluN1 available for ligand binding. Following CIS, Oxy-males (which did not acquire CPP) had increased GluN1 in all compartments of dendrites and spines of CA3 neurons. GluA1: There were no differences in the distribution GluA1 in any cellular compartments of CA3 dendrites in naïve females and males following either Sal or Oxy CPP. CIS alone increased the percent of GluA1 in CA3 dendritic spines in males compared to females. CIS Oxy-males compared to CIS Sal-males had an increase in cytoplasmic and total dendritic GluA1. Thus, in CIS Oxy-males increased pools of GluN1 and GluA1 are available for ligand binding in CA3 neurons. Together with our prior experiments, these changes in GluN1 and GluA1 following CIS in males may contribute to an increased sensitivity of CA3 neurons to glutamate excitation and a reduced capacity to acquire Oxy CPP.

Ketamine induced uropathy (KIU) is a urological condition increasing in prevalence, with similar symptoms to UTI, OAB syndrome or interstitial cystitis/bladder pain syndrome. We present the case of an 18-year old male who established severe LUTS and acute kidney injury due to KIU, in a short time-span of 6 months. Since cessation of ketamine is the cornerstone of treating KIU, correct and early diagnosis is essential. Physicians should therefore consider KIU as a differential diagnosis in storage LUTS, especially in younger patients with therapy-resistant LUTS.

Migraine results in an enormous burden on individuals and societies due to its high prevalence, significant disability, and considerable economic costs. Current treatment options for migraine remain inadequate, and the development of novel therapies is severely hindered by the incomplete understanding of the mechanisms responsible for the pain. The sensory innervation of the cranial meninges is now considered a key player in migraine headache genesis. Recent studies have significantly advanced our understanding of some of the processes that drive meningeal nociceptive neurons, which may be targeted therapeutically to abort or prevent migraine pain. In this review we will summarize our current understanding of the mechanisms that contribute to the genesis of the headache in one migraine subtype - migraine with aura. We will focus on animal studies that address the notion that cortical spreading depression is a critical process that drives meningeal nociception in migraine with aura, and discuss recent insights into some of the proposed underlying mechanisms.

UNASSIGNED: Posttraumatic epilepsy (PTE) is a serious and debilitating consequence of traumatic brain injury (TBI). Sometimes, the management of PTE becomes a challenging task on account of its resistance to existing antiepileptic drugs and often contributes to poor functional and psychosocial outcomes after TBI. We investigated the role of inflammatory markers interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (INF-γ) in predicting the development of PTE.
UNASSIGNED: A prospective analysis was performed of 254 patients who were admitted with head injury to our hospital, 35 of whom had posttraumatic epilepsy (32 males and 3 females); 30 adults (28 men, 2 women) with a similar demographic profile were selected randomly as control individuals. Blood levels of TNF-α, IL-6, and INF-γ were evaluated in all participants.
UNASSIGNED: IL-6 levels were significantly higher in the PTE group (121.36 pg/mL; standard deviation [SD], 89.23) than in the nonseizure group (65.30 pg/mL; SD, 74.75; P = 0.01), whereas there was no significant difference between the seizure group (11.42 pg/mL; SD, 7.84) and the nonseizure groups (10.58 pg/mL; SD, 7.84) in terms of TNF-α level (P = 0.343). The level of INF-γ in the seizure group tended to be higher (mean, 1.88 pg/mL, SD, 2.13 in seizure group vs. 1.10 pg/mL, SD, 1.45 in the nonseizure group); however, no statistically significant difference was detected among the 2 groups (P = 0.09).
UNASSIGNED: Posttraumatic epilepsy has a strong association with an increased level of IL-6 in the blood. INF-γ may or may not be associated with PTE. However, TNF-α was not associated with PTE.