Drug induced neurological disorders

High-fat diet (HFD)-induced systemic oxidative damage is critical to the pathological process of obesity and is associated with energy metabolism and cognitive disorders. In our previous research, the coumarin derivative Bis 3 was shown to improve neurological disorders as a potent free radical scavenger. In this study, a 12-week high-fat diet model was established, and mice were randomly divided into 3 groups: standard diet, high-fat diet, and high-fat diet with Bis 3 treatment. Our results demonstrated that Bis 3 attenuated body weight gain and inhibited the development of insulin resistance in high-fat diet-fed mice...

IMPORTANCE: Catamenial epilepsy (CE) is exacerbated by hormonal fluctuations during the menstrual cycle. Approximately 1.7 million women have epilepsy in the United States. CE affects more than 40% of women with epilepsy. There is a paucity of literature addressing this condition from a clinical standpoint, and the literature that does exist is limited to the neurological community. This article reviews the diagnosis and management of CE for the non-neurologist. Women with CE have early touch points in their care with numerous health care providers before ever consulting with a specialist, including OB/GYNs, pediatricians, emergency department physicians, and family medicine providers...

Multiple sclerosis (MS), as an inflammatory demyelinating disorder of central nervous system, is the leading cause of non-traumatic neurologic disability in young adults. The pathogenesis of MS remains unknown, however, a dysregulation of glia-neuroimmune signaling plays a key role during progressive disease stage. Most of the existing drugs are aimed at the immune system, but there is no approved drug by promoting remyelination after demyelination so far. There is a great interest in identifying novel agents for treating MS bytargeting to switch the immune imbalance from pro-inflammation and apoptosis to anti-inflammation and regeneration during remyelination phase...

BACKGROUND: Ionizing radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho-emotional balance, primarily an anxiogenic effect of IR. In our recent work we hypothesized that the neurokinin-1 (NK1) receptor may be instrumental for such alterations. OBJECTIVE: The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats...

Acute transverse myelitis (ATM) is a rare neurological condition that affects the spinal cord. Several events, including infections, autoimmune conditions, inflammatory, and drug-induced factors, may cause this disorder. Correct and rapid etiological diagnosis is necessary in order to start appropriate treatment that mainly consists of immunomodulating therapy, high dose intravenous corticosteroids, and in plasma exchange in noninfectious cases. The outcome is varied and depends on several factors. In children, the prognosis is usually good...

Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors (SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.2) likewise expressed in the pre-post synapsis of neurons and inflammatory cells, thereby affecting their proliferation and activity. KATP channels are involved in amyloid-β (Aβ)-induced pathology, therefore emerging as therapeutic targets against Alzheimer's and related diseases...

Substance use disorders are highly prevalent and continue to be one of the leading causes of disability in the world. Notably, not all people who use addictive drugs develop a substance use disorder. Although substance use disorders are highly heritable, patterns of inheritance cannot be explained purely by Mendelian genetic mechanisms. Vulnerability to developing drug addiction depends on the interplay between genetics and environment. Additionally, evidence from the past decade has pointed to the role of epigenetic inheritance in drug addiction...

Preclinical opioid research using animal models not only provides mechanistic insights into the modulation of opioid analgesia and its associated side effects, but also validates drug candidates for improved treatment options for opioid use disorder. Non-human primates (NHPs) have served as a surrogate species for humans in opioid research for more than five decades. The translational value of NHP models is supported by the documented species differences between rodents and primates regarding their behavioral and physiological responses to opioid-related ligands and that NHP studies have provided more concordant results with human studies...

BACKGROUND: Essential tremor is the most prevalent movement disorder and is thought to be caused by abnormalities in the cerebellar system; however, its underlying neural mechanism is poorly understood. In this study, we found that mice lacking netrin-G2, a cell adhesion molecule which is expressed in neural circuits related to the cerebellar system, exhibited a microtremor resembling an essential tremor. However, it was difficult to quantify microtremors in netrin-G2 KO mice. NEW METHOD: We developed a new tremor detector which can quantify the intensity and frequency of a tremor...

Mounting evidence suggests that modulation of cannabinoid 2 receptors (CB2Rs) is therapeutic in mouse models of neurological disorders, including neuropathic pain, neurodegenerative disease, and stroke. We previously showed that reducing CB2R activity increases seizure susceptibility in mice. In the present study, we evaluated the therapeutic potential of the CB2R positive allosteric modulator, Ec21a, against induced seizures in mice. The pharmacokinetic profile of Ec21 demonstrated a similar distribution in brain and plasma, with detection up to 12 hours following injection...

Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Sexual dysfunction has been reported in patients with seizure, which mostly manifests as erectile dysfunction and premature ejaculation in men. In this study, we report the case of a 65-year-old Chinese man with frequent spermatorrhea. Electroencephalography suggested local epilepsy in the left temporal lobe. After treatment with anti-epilepsy drugs, the symptoms disappeared and did not recur. To the best of our knowledge, this is the first reported case of epilepsy-induced spermatorrhea...

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency...

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease with low clinical penetrance, caused by mutations in the hydroxymethylbilane synthase ( HMBS ) gene, which encodes the third enzyme in the haem biosynthesis pathway. In susceptible HMBS mutation carriers, triggering factors such as hormonal changes and commonly used drugs induce an overproduction and accumulation of toxic haem precursors in the liver. Clinically, this presents as acute attacks characterised by severe abdominal pain and a wide array of neurological and psychiatric symptoms, and, in the long-term setting, the development of primary liver cancer, hypertension and kidney failure...

Treatment of chronic pain remains an unmet medical need. The neuronal voltage-gated potassium Kv7/KCNQ/M channel has been implicated as a therapeutic target for chronic pain. However, whether pharmacological activation of Kv7 channel can alleviate pain remains elusive. In this study, we show that selective activation of native M currents by a novel channel opener SCR2682 reduces repetitive firings of dorsal root ganglia (DRG) sensory neurons. Intraperitoneal administration of SCR2682 relieves mechanical allodynia and thermal hyperalgesia in rat models of pain induced by complete Freund's adjuvant (CFA) or spared nerve injury (SNI) in a dose-dependent manner without affecting locomotor activity...

The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses...

BACKGROUNDCisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss.METHODSWe examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy...

Somatic cells such as skin fibroblasts, umbilical cord blood, peripheral blood, urinary epithelial cells, etc., are transformed into induced pluripotent stem cells (iPSCs) by reprogramming technology, a milestone in the stem-cell research field. IPSCs are similar to embryonic stem cells (ESCs), exhibiting the potential to differentiate into various somatic cells. Still, the former avoid problems of immune rejection and medical ethics in the study of ESCs and clinical trials. Neurodevelopmental disorders are chronic developmental brain dysfunctions that affect cognition, exercise, social adaptability, behavior, etc...

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation...

Recently, it has been reported that dysfunction of astrocytes is involved vulnerability of neuronal cells in several neurological disorders. Glutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine is readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange transporter (xCT), GSH synthesis and release in/from surrounding astrocytes...

BACKGROUND & OBJECTIVE: Hyperalgesia and allodynia are frequent symptoms of inflammatory pain. Neuronal excitability induced by brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) cascade has a role in the modulation of inflammatory pain. The effects of 3a,4,5,9b-tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline8-sulfonamide (TQS), an α7 nicotinic acetylcholine receptor positive allosteric modulator (nAChR PAM), on hippocampal BDNF, cation-chloride cotransporters, NKCC1 and KCC2, expression in inflammatory pain are not known...