Low-Dose Taxol Promotes Neuronal Axons Extension and Functional Recovery after Spinal Cord Injury.

Axonal regeneration has been the research focus in the field of clinical treatment for spinal cord injury (SCI). The growth and extension of neuronal axons is a dynamic biological process mediated by the cytoskeleton, and microtubule plays an important role in axonal growth. Moderate stabilization of microtubule promotes axonal growth and eliminates various intra- and extracellular mechanisms that impede axonal regeneration. After SCI, the damaged axons rapidly form a growth cone, wherein the stability of tubulin decreases, impairing axonal regeneration. Taxol with proven clinical safety is commonly used as a broad-spectrum antitumor drug. Importantly, Taxol can promote axonal extension by enhancing and stabilizing the microtubule assembly. In our study, we systematically investigated the differentiation of neural stem cells (NSCs) in vitro and functional recovery in injured rats in vivo following Taxol treatment. Low-dose Taxol promoted differentiation of NSCs to neurons and significantly extended the axons in vitro. In vivo, Taxol promoted the expression of ßIII-tubulin in the injured areas and motor function recovery after SCI. Low-dose Taxol is a promising clinical agent to promote axonal regeneration after SCI.

Transmission and infection risk of COVID-19 when people coughing in an elevator.

People in cities use elevators daily. With the COVID-19 pandemic, there are more worries about elevator safety, since elevators are often small and crowded. This study used a proven CFD model to see how the virus could spread in elevators. We simulated five people taking in an elevator for 2 min and analyzed the effect of different factors on the amount of virus that could be inhaled, such as the infected person's location, the standing positions of the persons, and the air flow rate. We found that the position of the infected person and the direction they stood greatly impacted virus transmission in the elevator. The use of mechanical ventilation with a flow rate of 30 ACH (air changes per hour) was effective in reducing the risk of infection. In situations where the air flow rate was 3 ACH, we found that the highest number of inhaled virus copies could range from 237 to 1186. However, with a flow rate of 30 ACH, the highest number was reduced to 153 to 509. The study also showed that wearing surgical masks decreased the highest number of inhaled virus copies to 74 to 155.

Airborne transmission of COVID-19 virus in enclosed spaces: An overview of research methods.

Since the outbreak of COVID-19 in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has spread worldwide. This study summarized the transmission mechanisms of COVID-19 and their main influencing factors, such as airflow patterns, air temperature, relative humidity, and social distancing. The transmission characteristics in existing cases are providing more and more evidence that SARS CoV-2 can be transmitted through the air. This investigation reviewed probabilistic and deterministic research methods, such as the Wells-Riley equation, the dose-response model, the Monte-Carlo model, computational fluid dynamics (CFD) with the Eulerian method, CFD with the Lagrangian method, and the experimental approach, that have been used for studying the airborne transmission mechanism. The Wells-Riley equation and dose-response model are typically used for the assessment of the average infection risk. Only in combination with the Eulerian method or the Lagrangian method can these two methods obtain the spatial distribution of airborne particles' concentration and infection risk. In contrast with the Eulerian and Lagrangian methods, the Monte-Carlo model is suitable for studying the infection risk when the behavior of individuals is highly random. Although researchers tend to use numerical methods to study the airborne transmission mechanism of COVID-19, an experimental approach could often provide stronger evidence to prove the possibility of airborne transmission than a simple numerical model. All in all, the reviewed methods are helpful in the study of the airborne transmission mechanism of COVID-19 and epidemic prevention and control.

Application of data-driven RANS model in simulating indoor airflow.

The indoor environment has a significant impact on our wellbeing. Accurate prediction of the indoor air distribution can help to create a good indoor environment. Reynolds-averaged Navier-Stokes (RANS) models are commonly used for indoor airflow prediction. However, the Boussinesq hypothesis used in the RANS model fails to account for indoor anisotropic flows. To solve this problem, this study developed a data-driven RANS model by using a nonlinear model from the literature. An artificial neural network (ANN) was used to determine the coefficients of high-order terms. Three typical indoor airflows were selected as the training set to develop the model. Four other cases were used as testing sets to verify the generalizability of the model. The results show that the data-driven model can better predict the distributions of air velocity, temperature, and turbulent kinetic energy for the indoor anisotropic flows than the original RANS model. This is because the nonlinear terms are accurately simulated by the ANN. This investigation concluded that the data-driven model can correctly predict indoor anisotropic flows and has reasonably good generalizability.

Optical-feedback cavity ring-down spectroscopy for NO2 extinction coefficient measurement using a continuous wave laser diode.

Optical-feedback (OF) cavity ring-down spectroscopy consisting of a linear cavity is developed by employing a continuous wave laser diode (LD) with multi-longitudinal modes. Due to the OF effect caused by the cavity output laser back into the LD, the laser frequency is locked, and the intracavity laser intensity is enhanced. We use different concentrations of NO2 gases to test the apparatus, and the results show good agreement with theoretical values. Owing to the compactness of the laser source and high detection accuracy, the device can be used for detection of low-concentration absorbent gases in the environmental monitoring field.

Evaluation of airborne particle exposure for riding elevators.

Social distancing is a key factor for health during the COVID-19 pandemic. In many indoor spaces, such as elevators, it is difficult to maintain social distancing. This investigation used computational-fluid-dynamics (CFD) to study airborne particle exposure in riding an elevator in a typical building with 35 floors. The elevator traveled from the ground floor to the 35th floor with two stops on floor 10 and floor 20, comprising 114 s. The CFD simulated the dispersion of the aerosolized particles exhaled by an index person while breathing in both lobby and elevator areas. The study calculated the accumulated dose of susceptible riders riding in elevators with the index person under different conditions including different ventilation rates, air supply methods, and elevator cab geometries. This investigation also studied a case with a single cough from the index person as the person entered the elevator. The results show that, due to the short duration of the average elevator ride, the number of particles inhaled by a susceptible rider was low. For the reference case with a 72 ACH (air changes per hour) ventilation rate, the highest accumulated particle dose by a susceptible passenger close to the index person was only 1.59. The cough would cause other riders to inhale approximately 8 orders of magnitude higher particle mass than from continuous breathing by the index person for the whole duration of the ride.

Corrigendum to "Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk" Build. Environ., Volume 208, January 2022, 108590.

[This corrects the article DOI: 10.1016/j.buildenv.2021.108590.].

Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk.

The air distribution system in an airliner plays a key role in maintaining a comfortable and healthy environment in the aircraft cabin. To evaluate the performance of a novel displacement ventilation (DV) system and a traditional mixing ventilation (MV) system in an airliner cabin, this study conducted experiments and simulations in a seven-row cabin mockup. This investigation used ultrasonic anemometers and T-thermocouples to measure the air velocity, temperature and distribution of 1 µm and 5 µm particles. Simulation verifications were performed for these operating conditions, and additional scenarios with different occurrence source locations were also simulated. This study combined the Wells-Riley equation with a real case based on a COVID-19 outbreak among passengers on a long-distance bus to obtain the COVID-19 quanta value. Through an evaluation of the airflow organization, thermal comfort, and risk of COVID-19 infection, the two ventilation systems were compared. This investigation found that polydisperse particles should be used to calculate the risk of infection in airliner cabins. In addition, at the beginning of the pandemic, the infection risk with DV was lower than that with MV. In the middle and late stages of the epidemic, the infection risk with MV can be reduced when passengers wear masks, leading to an infection risk approximately equal to that of DV.

miR-942-5p promotes the proliferation and invasion of human melanoma cells by targeting DKK3.

OBJECTIVE: The purpose of this study was to figure out the dysregulation of miR-942-5p in melanoma and its role in melanoma pathogenesis. METHODS: Quantitative real-time PCR (qRT-PCR) assay was used to determine the change of RNA expression. Protein expression was examined by Western blotting. miRNA target was validated through TargetScan and luciferase assay. Cell migration and invasion were detected by wound healing and transwell assay, respectively. RESULTS: Results of qRT-PCR manifested miR-942-5p were upregulated in melanoma cell. High expression of miR-942-5p in melanoma patients presented a poor prognosis. Upregulation of miR-942-5p accelerated cell proliferation, migration, and invasion in melanoma cells. Cell apoptosis was inhibited by miR-942-5p mimics. Suppression of miR-942-5p by its inhibitor showed the opposite effects in melanoma cells. TargetScan and luciferase assay showed that miR-942-5p directly targeted to the 3'-untranslated region (3'-UTR) of DKK3. Overexpression of DKK3 inhibited GSK-3ß phosphorylation and reduced the expression of ß-catenin in both cytoplasm and nucleus, which were induced by miR-942-5p mimics leading to the activation of Wnt/ß-catenin pathway. CONCLUSION: Upregulation of miR-942-5p was observed in melanoma cells and tissues and significantly associated with a poor prognosis. Though targeting 3'-UTR of DKK3, miR-942-5p could activate Wnt/ß-catenin pathway, resulting in melanoma cell proliferation, migration, and invasion, which promoted the development of melanoma. These results showed that miR-942-5p might be a diagnosis and prognosis biomarker in melanoma.

Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury.

Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.

SIRT1 Mediates H2S-Ameliorated Diabetes-Associated Cognitive Dysfunction in Rats: Possible Involvement of Inhibiting Hippocampal Endoplasmic Reticulum Stress and Synaptic Dysfunction.

Diabetes-associated cognitive dysfunction (DACD) characterized by hippocampal injury increases the risk of major cerebrovascular events and death. Endoplasmic reticulum (ER) stress and synaptic dysfunction play vital roles in the pathological process. At present, no specific treatment exists for the prevention and/or the therapy of DACD. We have recently reported that hydrogen sulfide (H2S) exhibits therapeutic potential for DACD, but the underlying mechanism has not been fully elucidated. Silent information regulator 1 (SIRT1) has been shown to play a role in regulating the progression of diabetes and is also indispensable for memory formation and cognitive performance. Hence, the present study was performed to explore whether SIRT1 mediates the protective effect of H2S on streptozotocin (STZ)-induced cognitive deficits, an in vivo rat model of DACD, via inhibiting hippocampal ER stress and synaptic dysfunction. The results showed that administration of NaHS (an exogenous H2S donor) increased the expression of SIRT1 in the hippocampus of STZ-induced diabetic rats. Then, results proved that sirtinol, a special blocker of SIRT1, abrogated the inhibition of NaHS on STZ-induced cognitive deficits, as appraised by Morris water maze test, Y-maze test, and Novel object recognition behavioral test. In addition, administration of NaHS eliminated STZ-induced ER stress as evidenced by the decreases in the expressions of ER stress-related proteins including glucose-regulated protein 78, C/EBP homologous protein, and cleaved caspase-12 in the hippocampus, while these effects of NaHS were also reverted by sirtinol. Furthermore, the NaHS-induced up-regulation of hippocampal synapse-related protein (synapsin-1, SYN1) expression in STZ-induced diabetic rats was also abolished by sirtinol. Taken together, these results demonstrated that SIRT1 mediates the protection of H2S against cognitive dysfunction in STZ-diabetic rats partly via inhibiting hippocampal ER stress and synaptic dysfunction.

Inverse design of the thermal environment in an airplane cockpit using the adjoint method with the momentum method.

Currently, the thermal environment in airplane cockpits is unsatisfactory and pilots often complain about a strong draft sensation in the cockpit. It is caused by the unreasonable air supply diffusers design. One of the best approaches to design a better cockpit environment is the adjoint method. The method can simultaneously and efficiently identify the number, size, location, and shape of air supply inlets, and the air supply parameters. However, the real air diffuser needed to design often have grilles, especially in the airplane cockpit, and the current method can only design the inlet as an opening. This study combined the adjoint method with the momentum method to directly identify the optimal air supply diffusers with grilles to create optimal thermal environment in an airplane cockpit (1) under ideal conditions and (2) with realistic constraints. Under the ideal conditions, the resulting design provides an optimal thermal environment for the cockpit, but it might not be feasible in practice. The design with realistic constraints provides acceptable thermal comfort in the cockpit, but it is not optimal. Thus, there is an engineering trade-off between design feasibility and optimization. All in all, the adjoint method with the momentum method can be effectively used to identify real air supply diffusers.

Indoor thermal environment and air quality in Chinese-style residential kitchens.

This paper reviews the published literature on indoor thermal environment and air quality in Chinese-style residential kitchens (CRKs). The paper first discusses typical characteristics of CRKs, including kitchen layout, cooking methods, and ventilation systems used. Next, the paper describes the current state of the indoor thermal environment and air quality in CRKs. Finally, this paper summarizes measures to control and improve the environment inside CRKs. The results indicate that the indoor environment of CRKs is too hot in summer and exhibits a large vertical temperature difference. No appropriate model was available for accurately evaluating the thermal environment in CRKs. At the same time, CRKs are highly polluted by COx, NOx, TVOC, and particulate matter (PM). Although existing exhaust hoods could improve the indoor environment to some extent, the use of a combined exhaust, make-up air, and air-conditioning system should be considered to provide a comfortable and healthy environment in CRKs.

BDNF-TrkB pathway mediates antidepressant-like roles of H2 S in diabetic rats via promoting hippocampal autophagy.

Hydrogen sulfide (H2 S) plays antidepressant-like roles in diabetic rats. However, the underlying mechanisms remain unclear. Brain-derived neurotropic factor (BDNF), a neurotrophic factor, plays important regulatory roles in depression by its high-affinity tropomysin-related kinase B (TrkB) receptor. Autophagy also is implicated in modulation of depression. Previous work confirmed the modulatory roles of H2 S in BDNF protein expression and autophagy. Thus, in this study, we explored whether the BDNF-TrkB pathway mediates the antidepressant-like effects of H2 S in diabetic rats and whether this process is achieved via promoting hippocampal autophagy. We demonstrated that H2 S upregulated the expressions of BDNF and p-TrkB proteins in the hippocampus of streptozotocin (STZ)-induced diabetic rats. K252a (an inhibitor of BDNF-TrkB pathway) reversed the antidepressant-like roles of H2 S, as evidenced by the tail suspension, forced swimming, novelty suppressed feeding, and elevated plus-maze tests. Furthermore, K252a abolished H2 S-promoted hippocampal autophagy in diabetic rats, as evidenced by a decrease in the number of autolysosome, downregulation of Beclin-1 (a regulator of autophagy in the early stage of the formation of autophagosomal membranes and its level is positively correlated with autophagic activity) expression, and upregulation of P62 (a substrate of autophagic degradation and its level is inversely correlated with autophagic activity) expression, in the hippocampus of rats co-treated with NaHS and STZ. Taken together, these data indicated that the BDNF-TrkB pathway mediates the antidepressant-like roles of H2 S in diabetic rats by enhancing hippocampal autophagy.

Na+-K+-2Cl- symporter contributes to γ-aminobutyric acid-evoked excitation in rat enteric neurons.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the adult central nervous system (CNS), however, it causes excitation in the immature CNS neurons. The shift from GABA-induced depolarization to hyperpolarization in postnatal brain is primarily due to progressive decrease in the expression of the Na+-K+-2Cl- symporter 1 (NKCC1) and increased expression of the K+-Cl- cotransporter 2 (KCC2). Unlike CNS neurons, both immature and mature neurons in the enteric nervous system (ENS) are depolarized by GABA. Molecular mechanisms by which GABA excites ENS neurons are unclear. It is understood, however, that the excitatory action depends on elevated intraneuronal Cl-. We aimed to test a hypothesis that high intracellular Cl- in ENS neurons is maintained by activity of the NKCCs. We found that NKCC2 immunoreactivity (IR) was expressed in the ENS of the rat colon on postnatal day 1 (P1). The expression level of NKCC2 continuously increased and reached a steady high level on P14 and maintained at that level in adulthood. NKCC1 IR appeared in ENS on P14 and maintained through adulthood. KCC2 IR was not detectable in the ENS in any of the developmental stages. Both NKCC1 IR and NKCC2 IR were co-expressed with GABAA receptors in ENS neurons. Exogenous GABA (1 mmol/L) caused membrane depolarization in the ENS neurons. The reversal potential of GABA-induced depolarization was about -16 mV. Blockade of NKCC by bumetanide (50 µmol/L) or furosemide (300 µmol/L) suppressed the depolarizing responses to GABA. Bumetanide (50 µmol/L) shifted the reversal potential of GABA-induced depolarization in the hyperpolarizing direction. Neither the KCC blocker DIOA (20 µmol/L) nor the Cl-/HCO3- exchanger inhibitor DIDS (200 µmol/L) suppressed GABA-evoked depolarization. The results suggest that ENS neurons continuously express NKCC2 since P1 and NKCC1 since P14, which contribute to the accumulation of Cl- in ENS neurons and GABA-evoked depolarization in neonate and adult ENS neurons. These results provide the first direct evidence for the contribution of both NKCC2 and NKCC1 to the GABAA-mediated depolarization.

Prediction of particle deposition around the cabin air supply nozzles of commercial airplanes using measured in-cabin particle emission rates.

Enhanced soiling on the surfaces around air supply nozzles due to particle deposition is frequently observed in commercial airliners. The problem is worsened by severe outdoor air pollution and flight delays in China. The particles in an aircraft cabin originate from both outdoor and in-cabin sources. This study conducted measurements on multiple commercial flights to obtain particle emission rates from in-cabin sources. Additional experiments on a retired MD-82 airplane provided justification of the in-flight measurements. The in-cabin sources emitted more particles during boarding/deplaning than during meal servicing and sitting. The average PM2.5 emission rates were 7.2, 2.6, 1.9, and 1.8 (µg/min per person), respectively, during the boarding/deplaning, sitting on the ground, sitting in the air, and meal servicing. The corresponding PM10 emission rates were 15.4, 6.1, 5.3, and 5.4 (µg/min per person), respectively, for these four periods. The average particle emission rate from in-cabin sources varied seasonally and was the highest in winter. With the measured data, this investigation used a CFD model to predict the accumulation of particles deposited around the nozzles of an airplane, taking into account the flight routes and the outdoor particle concentrations at the airports where the airplanes were parked. For the most polluted airplane in China, the dirty spots/areas around the nozzles inside the airplane became visible after 6 months. The method proposed in this study can be used for any commercial airplane to predict the accumulation of particles deposited around the air supply nozzles.

Intrathecal Dexmedetomidine Alleviates Shivering during Cesarean Delivery under Spinal Anesthesia.

Shivering associated with spinal anesthesia during Cesarean delivery is an uncomfortable experience for the parturient, which may also cause adverse effects. In this prospective, randomized, double-blind, placebo-controlled study, we sought to evaluate the effect of intrathecal dexmedetomidine, administered as an adjunct to hyperbaric bupivacaine for Cesarean delivery, on the incidence and severity of shivering associated with spinal anesthesia. Patients undergoing Cesarean delivery were randomly allocated to three groups of 30 patients each. Experimental treatments were added to hyperbaric bupivacaine as follows: Patients in group I (control) were administered isotonic saline. Patients in groups II and III received dexmedetomidine (2.5, 5 µg, respectively), mixed with isotonic saline. Shivering was observed in 11, 10 and 2 patients in groups I, II and III, respectively. The incidence of shivering in group III was significantly lower than that in groups I (p=0.005) and II (p=0.01). The severity of shivering was significantly different between the three groups (p=0.01). There were no significant inter-group differences with respect to mean arterial pressure and heart rate at any time point after administration of intrathecal local anesthesia (p>0.05). Intrathecal dexmedetomidine (5 µg) administered as an adjunct to hyperbaric bupivacaine during Cesarean delivery significantly reduced the incidence and intensity of shivering associated with spinal anesthesia.

ß-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.

Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to ß-nicotinamide adenine dinucleotide (ß-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, ß-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. ß-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of ß-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of ß-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for ß-NAD at intestinal neuromuscular junctions. The data suggest that ß-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of ß-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions.

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²âº by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

Methylphenidate improves learning impairments and hyperthermia-induced seizures caused by an Scn1a mutation.

OBJECTIVE: Developmental disorders including cognitive deficit, hyperkinetic disorder, and autistic behaviors are frequently comorbid in epileptic patients with SCN1A mutations. However, the mechanisms underlying these developmental disorders are poorly understood and treatments are currently unavailable. Using a rodent model with an Scn1a mutation, we aimed to elucidate the pathophysiologic basis and potential therapeutic treatments for developmental disorders stemming from Scn1a mutations. METHODS: We conducted behavioral analyses on rats with the N1417H-Scn1a mutation. With high-performance liquid chromatography, we measured dopamine and its metabolites in the frontal cortex, striatum, nucleus accumbens, and midbrain. Methylphenidate was administered intraperitoneally to examine its effects on developmental disorder-like behaviors and hyperthermia-induced seizures. RESULTS: Behavioral studies revealed that Scn1a-mutant rats had repetitive behavior, hyperactivity, anxiety-like behavior, spatial learning impairments, and motor imbalance. Dopamine levels in the striatum and nucleus accumbens in Scn1a-mutant rats were significantly lower than those in wild-type rats. In Scn1a-mutant rats, methylphenidate, by increasing dopamine levels in the synaptic cleft, improved hyperactivity, anxiety-like behavior, and spatial learning impairments. Surprisingly, methylphenidate also strongly suppressed hyperthermia-induced seizures. SIGNIFICANCE: Dysfunction of the mesolimbic dopamine reward pathway may contribute to the hyperactivity and learning impairments in Scn1a-mutant rats. Methylphenidate was effective for treating hyperactivity, learning impairments, and hyperthermia-induced seizures. We propose that methylphenidate treatment may ameliorate not only developmental disorders but also epileptic seizures in patients with SCN1A mutations.