[Research Progress in the Correlation Between Dopamine and Clinical Characterization of Narcolepsy].

Dopamine,a neurotransmitter ubiquitous in the body fluids,blood,and urine of mammals and humans,is responsible for regulating their functions and metabolism.The dopamine system is involved in the neurobiological mechanisms of narcolepsy in animals and humans.However,researchers have drawn different or even opposite conclusions when measuring the dopamine level in the cerebrospinal fluid of narcolepsy patients.Studies have confirmed that the occurrence of narcolepsy is related to the irreversible loss of orexins.The autoimmune reaction caused by the interactions of environmental factors with genetic factors destroys the hypothalamic orexin neurons and reduces orexin secretion,thereby lowering the level of arousal.We introduce the research progress and current status of dopamine and clinical characterization of narcolepsy by reviewing more than 40 articles published from 1982 to 2023,aiming to provide a reference for studying the relationship between the dopamine level and clinical characterization of narcolepsy and searching for the biomarkers of type 2 narcolepsy.

Novel mutation of SPG4 gene in a Chinese family with hereditary spastic paraplegia: A case report.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of neurogenetic diseases of the corticospinal tract, accompanied by distinct spasticity and weakness of the lower extremities. Mutations in the spastic paraplegia type 4 (SPG4) gene, encoding the spastin protein, are the major cause of the disease. This study reported a Chinese family with HSP caused by a novel mutation of the SPG4 gene. CASE SUMMARY: A 44-year-old male was admitted to our hospital for long-term right lower limb weakness, leg stiffness, and unstable walking. His symptoms gradually worsened, while no obvious muscle atrophy in the lower limbs was found. Neurological examinations revealed that the muscle strength of the lower limbs was normal, and knee reflex hyperreflexia and bilateral positive Babinski signs were detected. Members of his family also had the same symptoms. Using mutation analysis, a novel heterozygous duplication mutation, c.1053dupA, p. (Gln352Thrfs*15), was identified in the SPG4 gene in this family. CONCLUSION: A Chinese family with HSP had a novel mutation of the SPG4 gene, which is autosomal dominant and inherited as pure HSP. The age of onset, sex distribution, and clinical manifestations of all existing living patients in this family were analyzed. The findings may extend the current knowledge on the existing mutations in the SPG4 gene.

Clinical safety and outcome of recombinant tissue plasminogen activator in patients with stroke attributable to small artery occlusion: A protocol for systematic review and meta-analysis.

BACKGROUND: Recent observations raised concern that the intravenous recombinant tissue plasminogen activator (rt-PA) may result in damage to stroke patients caused by small artery occlusion (SAO). Thus, we perform a protocol for meta-analysis to investigate the efficacy and safety of intravenous thrombolysis with rt-PA in SAO-patients. METHODS: The search-style electronic libraries, including Pubmed, Embase, the Cochrane Library, Web of Science, Wanfang Data, VIP Chinese Journals, and China Biomedical Literature Service System are used for document retrieval in June 2021 with no restrictions on language. The risk of bias in include articles will be assessed using the Cochrane Risk of Bias Tool. We perform the meta-analysis by Stata version 10.0 software and calculated the statistics using the inverse variance statistical method. Binary outcomes are presented as Mantel-Haenszel-style risk ratios with 95% confidence interval. Continuous outcomes are reported as mean differences. RESULTS: The results of the article will be shown in a peer-reviewed journal. CONCLUSION: Intravenous rt-PA may be effective and safe in SAO-patients.

[Research Progress on Insomnia and Microarousal].

Insomnia is a subjective experience of difficulty in falling asleep and/or maintaining sleep accompanied by the impairment of daytime social functioning due to insufficient sleep quality or quantity to meet normal physiological needs.It has chronic damage to all the human body systems and is the most common sleep disorder.The main mechanism for the occurrence and maintenance of insomnia is the hyperarousal hypothesis,and microarousal,as a cortical arousal,is also involved in the formation of the hyperarousal mechanism.The mechanism and clinical significance of microarousal were reviewed and summarized in this paper in order to guide the clinical work.

Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis.

Epilepsy is characterized by the occurrence of repetitive seizures and can greatly affect a patient's cognition, particularly in terms of learning and memory. Orexin-A is an excitatory neuropeptide produced by the lateral hypothalamus that has been shown to be involved in learning and memory. A reduction in the levels of orexin-A after seizures may underlie the learning and memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)-kindled rats to investigate the effects of orexin-A on learning and memory and the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2 activation. A Morris water maze test revealed reduced escape latencies, prolonged times in the target quadrant and an increased number of platform crossings in PTZ-kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on spatial learning and memory were attenuated by the intracerebroventricular injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats. However, these effects were inhibited by treatment with SB334867 or U0126. Taken together, these data suggest that orexin-A attenuated the impairment of spatial learning and memory in PTZ-kindled rats and that this attenuation involved neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation.

Pentylenetetrazol-induced seizures are exacerbated by sleep deprivation through orexin receptor-mediated hippocampal cell proliferation.

Sleep deprivation has been shown to be an activator of seizures in clinical and animal studies. Orexin-A was speculated to be involved in the aggravation of seizures by sleep deprivation through the activation of its receptors: orexin-1 and orexin-2 receptor (OX1R and OX2R, respectively). Therefore, we aimed to investigate the effects of pre-treating sleep-deprived Wistar rats with the OX1R or OX2R antagonists, SB334867 (30 nM/kg) or TCS OX2 29 (30 nM/kg), respectively, followed by a convulsive dose of 50 mg/kg pentylenetetrazol administration (seizure induction), on seizure behavior, and hippocampal neurodegeneration and cellular proliferation. Our results revealed that treatment with SB334867 or TCS OX2 29 significantly prolonged the latency and reduced the duration of seizures, while also lowering the mortality rate in sleep-deprived rats exposed to pentylenetetrazol. In addition, SB334867 or TCS OX2 29 reduced the damage to hippocampal CA3 neurons and the number of bromodeoxyuridine-positive cells in the dentate gyrus (particularly in the hilus). Overall, the effect of TCS OX2 29 was greater than that of SB334867. Taken together, these data suggest that OX1R and OX2R antagonists may alleviate the damage of pentylenetetrazol-induced seizures that are exacerbated by sleep deprivation, and furthermore could be associated with a reduction of neuronal damage in the hippocampus and the inhibition of cellular proliferation in the dentate gyrus.