Lentivirus carrying the Atoh1 gene can infect Corti’s organ and express a hair-like cell surface marker in the supporting cell area. However, expression of the gene carried by adenovirus is instantaneous, which undoubtedly limits its clinical application. Lentivirus acts as a carrier that can stably and continuously express genes. In this study, the cochlear structure and hearing level were not affected, and Atoh1 gene carried by lentivirus promoted the production of hair-like cells in the cochlear supporting cell area. This led to expression of the hair-like cell surface marker myosin 7a 30 days after lentivirus carrying Atoh1 was microinjected into the cochlear round window of rats.
(1) Numbers of hair cells and auditory function in normal rats were observed after microinjection of lentivirus carrying enhanced green fluorescent protein and Atoh1 into the rat cochlea, and the production of new hair cells in cochlea was explored.
(2) Recombinant lentivirus carrying a reporter gene, enhanced green fluorescent protein, and the target gene Atoh1 were constructed by gene engineering methods. Then, recombinant lentivirus was injected into the cochlea of normal rats using a postauricular approach via the round window membrane. The results showed that recombinant lentivirus has no impact on the hair cell numbers and auditory functions, can infect hair and supporting cells, and promotes supporting cells to transdifferentiate into hair cells.
(3) Recombinant lentivirus carrying enhanced green fluorescent protein and the Atoh1 gene caused no obvious damage to cochlear hair cells or auditory function. The target gene carried in lentivirus was continuously expressed in the transfected cells, providing evidence for lentivirus research.
Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by three additional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal rats injected with equivalent volumes of saline served as controls. Hippocampal samples were collected at 1, 7 or 14 days following administration. Electron microscopy showed that neuronal structure changed noticeably following ketamine treatment. Specifically, microtubular structure became irregular and disorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulated after ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396 initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At 14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in the control group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection, and then gradually decreased with time. However, the levels of tau protein at serine 404 were significantly greater in the ketamine group than in the control group until 14 days. The present results indicate that ketamine induces an increase of phosphorylated tau mRNA and excessive phosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rat hippocampus and potentially resulting in damage to hippocampal neurons.
(1) Commonly used inhalation anesthetics such as isoflurane and sevoflurane can induce apoptosis, tau protein hyperphosphorylation and memory disorders.
(2) Tau protein hyperphosphorylation at serine 396/serine 404 is found in intraneuronal neurofibrillary tangles during neurodegeneration.
(3) Hyperphosphorylated tau protein at serine 396 has been found in adult monkey brain tissue following chronic ketamine administration.
(4) We show that hyperphosphorylation of tau protein at serine 404, but not serine 396, occurs in neonatal rat hippocampus following a large dose of ketamine.
(5) Our results suggest that ketamine induces tau hyperphosphorylation at serine 404, resulting in damage to microtubule and axonal transport. Such damage may cause neurotoxicity and neuronal death in neonatal rats, consistent with previous studies demonstrating ketamine-induced neuronal apoptosis.
There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.
(1) There is increasing clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients.
(2) This article reviews in vivo and in vitro studies of chemotherapy-induced neurodegeneration and hippocampal dysfunctions, and related mechanisms.
To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.
(1) This retrospective clinical controlled study demonstrated that dissecting the recurrent laryngeal nerve during thyroid surgery is clinically significant for preventing nerve injury.
(2) Dissecting the recurrent laryngeal nerve during thyroid surgery can effectively prevent nerve injury in the presence of anatomical variations.
(3) The inferior parathyroid gland is an optimal anatomical landmark for locating the recurrent laryngeal nerve during thyroid surgery.
(4) The middle thyroid vein is also an important anatomical landmark of dissecting the recurrent laryngeal nerve.
Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.
(1) Initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B6 and immunoglobulin in 51 children newly diagnosed with infantile spasms significantly improved their rate of seizures and electroencephalographic hypsarrhythmia, with low relapse and no severe adverse effects.
(2) The effects of this polytherapy in cryptogenic children were superior to symptomatic children.
Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin (p38) mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.
(1) Increasing evidence indicates that exogenous neuropeptide Y can suppress epileptic seizures. However, the most effective administration route of exogenous neuropeptide Y remains unclear.
(2) Adeno-associated virus was used as a vector to explore the effect of neuropeptide Y gene transfection on hippocampal mossy fibers, which undergo post-epileptic synaptic reconstruction.
(3) Neuropeptide Y gene transfection was found to inhibit mossy fiber sprouting.
X-irradiation has a beneficial effect in treating spinal cord injury. We supposed that X-irradiation could improve the microenvironment at the site of a spinal cord injury and inhibit glial scar formation. Thus, this study was designed to observe the effects of 8 Gy X-irradiation on the injury site at 6 hours and 2, 4, 7, and 14 days post injury, in terms of improvement in the microenvironment and hind limb motor function. Immunohistochemistry showed that the expression of macrophage marker ED-1 and the area with glial scar formation were reduced. In addition, the Basso, Beattie and Bresnahan score was higher at 7 days post injury relative to the other time points post injury. Results indicated that X-irradiation at a dose of 8 Gy can inhibit glial scar formation and alleviate the inflammatory reaction, thereby repairing spinal cord injury. X-irradiation at 7 days post spinal cord injury may be the best time window.
(1) The glial scar is the main inhibitor of axon regeneration and functional recovery in the central nervous system. X-irradiation has been shown to inhibit the formation of glial scars post injury and can promote injury repair.
(2) This study investigated the effects of X-irradiation at different time points on the formation of the glial scar and its influence on the neurological function in rats post injury. Results confirmed that X-irradiation at a dose of 8 Gy can inhibit glial scar formation at the injury site and alleviate the inflammatory reaction. Day 7 post injury may be the optimal time window for topical X-irradiation.
Parkinson’s disease has a negative impact on health-related quality of life in Parkinson’s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson’s disease patients in northeastern Sicily, Italy. Ninety Parkinson’s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi “Bonino-Pulejo” (Messina), were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale (UPDRS-III) scores, the Parkinson Disease Questionnaire-39 Item scores (as a disease-specific measure of health-related quality of life), scores on the Short Form (36) Health Survey Questionnaire (as a generic measure), and answers to a brief checklist were recorded. A total of 85 Parkinson’s disease patients (49% males and 51% females; mean age 70.8 ± 8.6 years; mean UPDRS-III 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years) completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.
(1) Parkinson’s disease has a negative impact on patients’ health-related quality of life.
(2) Within an ecological framework, intrapersonal and interpersonal aspects may have a compounding effect on health-related quality of life outcomes.
(3) Gender, self-evaluated autonomy and family size significantly impact health-related quality of life in people with Parkinson’s disease.
(4) An ecological framework is important for determining personalized health care interventions and improving medical decision making.
The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.
(1) The neurites of cochlear neurons grew readily from spiral ganglion explants through collagen gels in culture.
(2) Co-culture with fibroblasts producing neurotrophin-3 stimulated the growth of neurites from cochlear neurons, and enhanced their survival, although the fibroblasts were not targeted.
(3) Cells producing brain-derived neurotrophic factor enhanced spiral ganglion neuron survival, but not neurite extension, although the cells were not targeted.
(4) A combination of collagen gels and neurotrophin-secreting cells could enhance spiral ganglion neuron survival and draw neurites toward a cochlear implant.
Studies have shown that there are strong interactions between gustatory and visceral sensations in the central nervous system when rats ingest sweet foods or solutions. To investigate the role of the subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats deprived of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water.
(1) Previous studies in rats have focused on the effects of subdiaphragmatic vagotomy on the intake of solid foods, but not sweet-tasting solutions.
(2) This study highlights the influence of subdiaphragmatic vagotomy on the intake of sweet-tasting solutions such as sucrose and saccharin. Sucrose intake increased transmission of general visceral information, while saccharin intake reduced transmission.
(3) This study also investigated the influence of subdiaphragmatic vagotomy on body mass gain over a short period of time, in contrast with the long period of time observed in previous studies.
(4) The vagal and humoral pathways transmitting visceral information play a reciprocal-balancing role. Functional loss of the vagus nerve enhances negative feedback signals from the gastrointestinal tract and eliminates the differences in hedonic perception induced by sweet-tasting solutions compared with distilled water. In addition, subdiaphragmatic vagotomy has minimal effects on body mass gain over a short period of time.
This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.
(1) Mechanical strain contributes to the formation of hyperplastic scar in wounds.
(2) Nerve density and expression of nerve growth factor are increased in hyperplastic scar tissue.
(3) The cutaneous nervous system is involved in mechanical strain-caused hypertrophic scar development.