Sustancia Cromatofílica: Una Propuesta de Cambio a la Terminologia Histologica y Terminologia Neuroanatomica / Chromatophilic Substance: a Proposal to Change the Terminologia Histologica and Terminologia Neuroanatomica

En Terminologia Histologica y Terminologia Neuroanatomica está registrado el término Substantia chromatophilica de origen grecolatino, con los códigos H2.00.06.1.00009 y 78, respectivamente. Dicho término ha sido empleado para referirse a un conglomerado de estructuras que en unión fungen como maquinaria de síntesis proteica y que son característicos de las células nerviosas. Teniendo en cuenta los lineamientos de la Federative International Programme for Anatomical Terminology (FIPAT) referentes a la denominación de nombres estructurales con un valor descriptivo e informativo, creemos que el término en cuestión no es el más adecuado. Por lo anterior, el objetivo del presente estudio fue analizar y evaluar la concordancia de las raíces grecolatinas que componen el término. Para ello, se llevó a cabo una búsqueda en el Diccionario de la lengua española, Diccionario de Términos Médicos, diccionario VOX Griego-Español y el diccionario VOX Ilustrado Latino-Español Español-Latino. Los resultados obtenidos indican que la palabra chromatophilica no presenta registro en español, sin embargo, sus sinónimos hacen referencia a material biológico afín por los colorantes. En base a lo anterior, proponemos el término Ribocumulus corponeuralis en función de su estructura y ubicación, en reemplazo de Substantia chromatophilica.

SUMMARY: In Terminologia Histologica and Terminologia Neuroanatomica the term Substantia chromatophilica of Greco-Latin origin is registered with the codes H2.00.06.1.00009 and 78, respectively. This term has been used to refer to a conglomerate of structures that together function as protein synthesis machinery and are characteristic of nerve cells. Considering the guidelines of the Federative International Programme for Anatomical Terminology (FIPAT) regarding the denomination of structural names with a descriptive and informative value, we believe that the term in question is not the most appropriate. Therefore, this study aimed to analyze and evaluate the concordance of the Greco-Latin roots that compose the term. For this purpose, a search was conducted in the Diccionario de la Lengua Española, Diccionario de Términos Médicos, Diccionario VOX Griego-Español and the Diccionario VOX Ilustrado Latino-Español Español-Latino. The results obtained indicate that the word chromatophilica is not registered in Spanish, however, its synonyms refer to biological material related to dyes. Based on the aforementioned, we propose the term Ribocumulus corponeuralis based on its structure and location, as a replacement for Substantia chromatophilica.

An experimental study of tangzhouling on morphological changes of nissl bodies in the dorsal root ganglion of DM rats / Un estudio experimental de tangzhouling sobre los cambios morfológicos de los cuerpos de nissl en el ganglio de la raíz dorsal de ratas DM

SUMMARY: This study aims to investigate the effect of Tangzhouling on the morphological changes of Nissl bodies in the dorsal root ganglion of DM Rats. In this study, 69 rats were randomly divided into a control group (n = 10) and a model group (n = 59). The rats in the model group were randomly divided into a diabetic group (n = 11), a vitamin C group (n = 12), a low dose Tangzhouling group (n = 12), a medium dose Tangzhouling group (n = 12) and a high dose Tangzhouling group (n = 12). The dose of Tangzhouling in the low dose group was 5 times that of the adult dose, being 0.44g/kg/d. The dose of Tangzhouling in the medium dose group was 10 times that of the adult dose, being 0.88g/kg/d. The dose of Tangzhouling in the high dose group was 20 times that of the adult dose, being 1.75g/kg/d. All doses above are crude drug dosages. Rats in the vitamin C group were given 10 times the dose of an adult, being, 0.05 g/ kg/d. The diabetic group and the control group were given the same amount of distilled water. Drug delivery time is 16 weeks. The dorsal root ganglion was placed in a freezing tube at the end of the experiment. The morphological changes of Nissl bodies in the dorsal root ganglion were detected by HE and Nissl staining. The study results showed that vitamin C had no significant effect on the quantity, size and nucleolus. Tangzhouling can improvee the morphology, quantity and nucleolus of Nissl bodies to a certain extent, and the high dose is better than the lower dose. Tangzhouling capsules can improve the nerve function of DM rats through Nissl bodies.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de Tangzhouling en los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal de las ratas DM. En este estudio, 69 ratas se dividieron aleatoriamente en un grupo control (n = 10) y un grupo modelo (n = 59). Las ratas del grupo modelo se dividieron aleatoriamente en un grupo diabéticos (n = 11), un grupo vitamina C (n = 12), un grupo de dosis baja de Tangzhouling (n = 12), un grupo de dosis media de Tangzhouling (n = 12) y un grupo de dosis alta de Tangzhouling (n = 12). La dosis de Tangzhouling en el grupo de dosis baja fue 5 veces mayor que la dosis del adulto, siendo 0,44 g/kg/d. La dosis de Tangzhouling en el grupo de dosis media fue 10 veces mayor que la dosis del adulto, siendo 0,88 g/kg/d. La dosis de Tangzhouling en el grupo de dosis alta fue 20 veces mayor que la dosis del adulto, siendo 1,75 g/kg/d. Todas las dosis anteriores son dosis de fármaco crudo. Se les administró 10 veces la dosis de un adulto a las ratas del grupo vitamina C, siendo 0,05 g/kg/d. El grupo de diabéticos y el grupo de control recibieron la misma cantidad de agua destilada. El tiempo de entrega del fármaco fue de 16 semanas. El ganglio de la raíz dorsal se colocó en un tubo de congelación al final del experimento. Los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal se detectaron mediante tinción de HE y Nissl. Los resultados del estudio mostraron que la vitamina C no tuvo un efecto significativo sobre la cantidad, el tamaño y el nucléolo. Tangzhouling puede mejorar la morfología, la cantidad y el nucléolo de los cuerpos de Nissl hasta cierto punto, y es mejor la dosis alta que la dosis baja. Las cápsulas de Tangzhouling pueden mejorar la función nerviosa de las ratas DM a través de los cuerpos de Nissl.

Protective effects of hydroxy-α-sanshool from the pericarp of Zanthoxylum bungeanum Maxim. On D-galactose/AlCl3-induced Alzheimer's disease-like mice via Nrf2/HO-1 signaling pathways.

Hydroxy-α-sanshool (HAS) is an unsaturated fatty acid amide from Zanthoxylum bungeanum Maxim. with hypolipidemic, hypoglycemic, anti-inflammatory, and neurotrophic effects, etc. In this study, results indicated that HAS effectively ameliorated spontaneous locomotion deficit of mice induced by D-galactose (D-gal) and AlCl3 treatment in open field test. Results of Morris water maze test (MWM) showed that HAS significantly improved the spatial learning and memory ability of aging mice. Histopathological evaluations revealed that HAS markedly alleviated morphological changes and increased number of Nissl neurons in hippocampus of D-gal/AlCl3-induced Alzheimer's disease (AD)-like mice. HAS markedly reduced malondialdehyde (MDA) production, and increased the activity of antioxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), showing an inhibitory effect on oxidative stress. Furthermore, HAS treatment obviously reversed the inhibitory expressions of mRNA and protein of HO-1 and Nrf2 in the hippocampus of AD mice, suggesting that neuroprotective effects of HAS against oxidative stress might be mediated by the Nrf2/HO-1 pathway. Meanwhile, HAS significantly inhibited neuronal apoptosis by decreasing mRNA and protein expressions of Cyt-c, Bax and Caspase 3, and increasing Bcl-2 expression in the hippocampus of AD mice. These results suggest that HAS have the potential to be developed as antioxidant drug for the prevention and early therapy of AD.

Silver Nanoparticles Conjugate Attenuates Highly Active Antiretroviral Therapy-Induced Hippocampal Nissl Substance and Cognitive Deficits in Diabetic Rats.

BACKGROUND: The application of nanomedicine to antiretroviral drug delivery holds promise in reducing the comorbidities related to long-term systemic exposure to highly active antiretroviral therapy (HAART). However, the safety of drugs loaded with silver nanoparticles has been debatable. This study is aimed at evaluating the effects of HAART-loaded silver nanoparticles (HAART-AgNPs) on the behavioural assessment, biochemical indices, morphological, and morphometric of the hippocampus in diabetic Sprague-Dawley rats. METHODS: Conjugated HAART-AgNPs were characterized using FTIR spectroscopy, UV spectrophotometer, HR-TEM, SEM, and EDX for absorbance peaks, size and morphology, and elemental components. Forty-eight male SD rats (250 ± 13 g) were divided into nondiabetic and diabetic groups. Each group was subdivided into (n = 8) A (nondiabetic+vehicle), B (nondiabetic+HAART), C (nondiabetic+HAART-AgNPs), D (diabetic+vehicle), E (diabetic+HAART), and F (diabetic+HAART-AgNPs). Morris water maze, Y-maze test, and weekly blood glucose levels were carried out. Following the last dose of 8-week treatment, the rats were anaesthetized and euthanized. Brain tissues were carefully removed and postfixed for Nissl staining histology. RESULTS: 1.5 M concentration of HAART-AgNPs showed nanoparticle size 20.3 nm with spherical shape. HAART-AgNPs revealed 16.89% of silver and other elemental components of HAART. The diabetic control rats showed a significant increase in blood glucose, reduced spatial learning, positive hippocampal Nissl-stained cells, and a significant decrease in GSH and SOD levels. However, administration of HAART-AgNPs to diabetic rats significantly reduced blood glucose level, improved spatial learning, biochemical indices, and enhanced memory compared to diabetic control. Interestingly, diabetic HAART-AgNP-treated rats showed a significantly improved memory, increased GSH, SOD, and number of positive Nissl-stained neurons compared to diabetic-treated HAART only. CONCLUSION: Administration of HAART to diabetic rats aggravates the complications of diabetes and promotes neurotoxic effects on the experimental rats, while HAART-loaded silver nanoparticle (HAART-AgNP) alleviates diabetes-induced neurotoxicity.

Endoplasmic Reticulum Stress Is Associated with the Mesencephalic Dopaminergic Neuron Injury in Stressed Rats.

An increasing number of people are in a state of stress due to social and psychological pressures, which may result in mental disorders. Previous studies indicated that mesencephalic dopaminergic neurons are associated with not only reward-related behaviors but also with stress-induced mental disorders. To explore the effect of stress on dopaminergic neuron and potential mechanism, we established stressed rat models of different time durations and observed pathological changes in dopaminergic neurons of the ventral tegmental area (VTA) through HE and thionine staining. Immunohistochemistry coupled with microscopy-based multicolor tissue cytometry (MMTC) was employed to investigate the number changes of dopaminergic neurons. Double immunofluorescence labelling was used to investigate expression changes of endoplasmic reticulum stress (ERS) protein GRP78 and CHOP in dopaminergic neurons. Our results showed that prolonged stress led to pathological alteration in dopaminergic neurons of VTA, such as missing of Nissl bodies and pyknosis in dopaminergic neurons. Immunohistochemistry with MMTC indicated that chronic stress exposure resulted in a significant decrease in dopaminergic neurons. Double immunofluorescence labelling showed that the endoplasmic reticulum stress protein took part in the injury of dopaminergic neurons. Taken together, these results indicated the involvement of ERS in mesencephalic dopaminergic neuron injury induced by stress exposure.

Role of melatonin in the dynamics of acute spinal cord injury in rats.

Melatonin is well-documented to have the ability of reducing nerve inflammation and scavenging free radicals. However, the therapeutic effect of melatonin on spinal cord injury has not been fully described. In this study, we assessed the effect of melatonin on T9 spinal cord injury established by Allen method in rats. Melatonin deficiency significantly delayed the recovery of sensory and motor functions in SCI rats. Treatment with melatonin significantly alleviated neuronal apoptosis and accelerated the recovery of spinal cord function. These results suggest that melatonin is effective to ameliorate spinal cord injury through inhibition of neuronal apoptosis and promotion of neuronal repair.

Time-Dependent Memory and Gait Improvement by Intranasally-Administered Extracellular Vesicles in Parkinson's Disease Model Rats.

We have recently demonstrated that extracellular vesicles (EVs) derived from the human teeth stem cells improve motor symptoms and normalize tyrosine hydroxylase (TH) expression in the nigrostriatal structures of Parkinson's disease (PD) model rats obtained by 6-hydroxydopamine (6-OHDA) unilateral injection into the medial forebrain bundle (MFB). The aim of this study was to clarify: (1) how long therapeutic effects persist after discontinuation of 17-day intranasal administration of EVs in 6-OHDA rats; (2) may EVs reverse cognitive (learning/memory) dysfunction in these PD model rats; (3) whether and how the behavioral improvement may be related to the expression of TH and Nissl bodies count in the nigrostriatal structures. Our results demonstrated that in 6-OHDA rats, gait was normalized even ten days after discontinuation of EVs administration. EVs successfully reversed 6-OHDA-induced impairment in spatial learning/memory performance; however, the beneficial effect was shorter (up to post-treatment day 6) than that revealed for gait improvement. The shorter effect of EVs coincided with both full normalization of TH expression and Nissl bodies count in the nigrostriatal structures, while slight but significant increase in the 6-OHDA-decreased Nissl count persisted in the substantia nigra even on the post-treatment day 20, supposedly due to the continuation of protein synthesis in the living cells. The obtained data indicate the usefulness of further studies to find the optimal administration regimen which could be translated into clinical trials on PD patients, as well as to clarify other-apart from dopaminergic-neuromodulatory pathways involved in the EVs mechanism of action.

Evaluation of the effect of myelotomy on nerve function in rats with spinal cord injury by diffusion tensor imaging.

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system injury that can generally induce different degrees of sensory and motor dysfunction. PURPOSE: To clarify the changes of diffusion tensor imaging (DTI) parameters after spinal cord myelotomy in rats with SCI. MATERIAL AND METHODS: Eighteen Sprague Dawley (SD) rats were randomly divided into the Sham group (n=6), SCI group (n=6), and Mye group (n=6), respectively. The DTI values at 1, 3, 7, and 21 days after modeling were collected by magnetic resonance imaging (MRI). The spinal specimen at the injury site was collected on the 21st day for Nissl's staining to assess the changes in neurons. RESULTS: The fractional anisotropy (FA) values in both the SCI group and Mye group significantly decreased. In addition, the FA values between the two groups were statistically significant (P < 0.001). The apparent diffusion coefficient (ADC), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values all decreased and then increased (P < 0.001). Pearson correlation test showed that the ADC, MD, and AD values were positively correlated with the Basso Beattie Bresnahan (BBB) score. Nissl's staining showed a higher number of Nissl's bodies, and deep staining of Nissl's bodies in the Mye group, while the morphology of neurons was relatively good. The number of neurons in the Mye group was significantly higher after myelotomy compared to the SCI group (P < 0.001). CONCLUSION: The DTI parameters, especially ADC values, could non-invasively and quantifiably evaluate the efficacy of myelotomy for rats with SCI.

The Human and Mouse Enteric Nervous System at Single-Cell Resolution.

The enteric nervous system (ENS) coordinates diverse functions in the intestine but has eluded comprehensive molecular characterization because of the rarity and diversity of cells. Here we develop two methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling. The 1,187,535 nuclei in our mouse atlas include 5,068 neurons from the ileum and colon, revealing extraordinary neuron diversity. We highlight circadian expression changes in enteric neurons, show that disease-related genes are dysregulated with aging, and identify differences between the ileum and proximal/distal colon. In humans, we profile 436,202 nuclei, recovering 1,445 neurons, and identify conserved and species-specific transcriptional programs and putative neuro-epithelial, neuro-stromal, and neuro-immune interactions. The human ENS expresses risk genes for neuropathic, inflammatory, and extra-intestinal diseases, suggesting neuronal contributions to disease.

Cortex Mori Radicis extract promotes neurite outgrowth in diabetic rats by activating PI3K/AKT signaling and inhibiting Ca2+ influx associated with the upregulation of transient receptor potential canonical channel 1.

Cortex Mori Radicis extract (CMR) has various pharmacological properties, such as anti­inflammatory, anti­allergic and anti­hyperglycemic effects. However, the effects and mechanisms of CMR in the neuroregeneration of diabetic peripheral neuropathy (DPN) are unclear. In the present study, the effects of CMR on neurite outgrowth of dorsal root ganglia (DRG) neurons in diabetic rats were investigated and its underlying mechanisms were explored. SD rats were subjected to a high­fat diet with low­dose streptozotocin to induce a Type II diabetes model with peripheral neuropathy. CMR was then applied for four weeks continuously with or without injection of small interfere (si)RNA targeting the transient receptor potential canonical channel 1 (TRPC1) via the tail vein. Blood glucose levels, the number of Nissl bodies, neurite outgrowth and growth cone turning in DRG neurons were evaluated. The expression of TRPC1 protein, Ca2+ influx and activation of the PI3K/AKT signaling pathway were also investigated. The results of the present study showed that CMR significantly lowered blood glucose levels, reversed the loss of Nissl bodies, induced neurite outgrowth and restored the response of the growth cone of DRG neurons in diabetic rats. CMR exerted neurite outgrowth­promoting effects by increasing TRPC1 expression, reducing Ca2+ influx and enhancing AKT phosphorylation. siRNA targeting TRPC1 in the CMR group abrogated its anti­diabetic and neuroregenerative effects, suggesting the involvement of TRPC1 in the biological effects of CMR on DPN.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure.

OBJECTIVE: To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. METHODS: One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. RESULTS: The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB. CONCLUSION: Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Activation of the MAPK signaling pathway induces upregulation of pro-apoptotic proteins in the hippocampi of cold stressed adolescent mice.

Stress induces many non-specific responses in the hippocampus, especially during adolescence. Low environmental temperature is known to induce stress, but its influence on the hippocampus, especially in adolescent mice is not clear. We compared apoptotic-related protein levels and MAPK signaling pathway activation in hippocampal neurons of adolescent mice under low temperature conditions (4 °C for 12 h) with western blotting and immunohistochemistry. Western bolt results demonstrated that the levels of phospho-JNK, phospho-p38, and cleaved-caspase 3 significantly increased, while the ratio of Bcl-XL/Bax decreased, in the cold stress group. The results of immunohistochemistry (IHC) and Nissl staining demonstrated that the protein optical density of caspase 3 increased and Nissl bodies decreased in the cold stress group compared with controls. Thus, we conclude that cold exposure initiates activation of the MAPK signaling pathway and subsequently induces the upregulation of pro-apoptotic proteins in the hippocampi of adolescent mice. Overall our study reveals the relationship between cold stress and apoptosis in adolescent mice.

Dendrobium officinale polysaccharides attenuate learning and memory disabilities via anti-oxidant and anti-inflammatory actions.

The aim of this study was to explore the therapeutic effect and underling mechanism of Dendrobium officinale polysaccharides (DOPS) on two well-established animal models of learning and memory disabilities. Model of estrogen deficiency caused learning and memory disability can be induced by ovariectomy in mice, and mice were injected subcutaneously with d-galactose, which can also cause cognitive decline. H&E staining and Nissl staining were employed to confirm the protective effect of DOPS on hippocampal neuron. Morris water maze test, biochemical analysis, immunohistochemistry and immunofluorescence assay were used to study the effect and underlying mechanism of DOPS on two different learning and memory impairment models. Administration of DOPS significantly improved learning and memory disability in both models. Further studies showed that DOPS could attenuate oxidative stress and reduce neuro-inflammation via up-regulating expressions of Nrf2/HO-1 pathway and inhibiting activation of astrocytes and microglia in ovariectomy- and d-galactose-induced cognitive decline. These findings suggest that DOPS have an appreciable therapeutic effect on learning and memory disabilities and its mechanism may be related to activate Nrf2/HO-1 pathway to reduce oxidative stress and neuro-inflammation.

Colocalization of neurons in optical coherence microscopy and Nissl-stained histology in Brodmann's area 32 and area 21.

Optical coherence tomography is an optical technique that uses backscattered light to highlight intrinsic structure, and when applied to brain tissue, it can resolve cortical layers and fiber bundles. Optical coherence microscopy (OCM) is higher resolution (i.e., 1.25 µm) and is capable of detecting neurons. In a previous report, we compared the correspondence of OCM acquired imaging of neurons with traditional Nissl stained histology in entorhinal cortex layer II. In the current method-oriented study, we aimed to determine the colocalization success rate between OCM and Nissl in other brain cortical areas with different laminar arrangements and cell packing density. We focused on two additional cortical areas: medial prefrontal, pre-genual Brodmann area (BA) 32 and lateral temporal BA 21. We present the data as colocalization matrices and as quantitative percentages. The overall average colocalization in OCM compared to Nissl was 67% for BA 32 (47% for Nissl colocalization) and 60% for BA 21 (52% for Nissl colocalization), but with a large variability across cases and layers. One source of variability and confounds could be ascribed to an obscuring effect from large and dense intracortical fiber bundles. Other technical challenges, including obstacles inherent to human brain tissue, are discussed. Despite limitations, OCM is a promising semi-high throughput tool for demonstrating detail at the neuronal level, and, with further development, has distinct potential for the automatic acquisition of large databases as are required for the human brain.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms.@*METHODS@#One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure.@*RESULTS@#The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB.@*CONCLUSION@#Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Corilagin Reduces the Frequency of Seizures and Improves Cognitive Function in a Rat Model of Chronic Epilepsy.

BACKGROUND Worldwide, epilepsy is an important chronic neurological condition. The aim of this study was to evaluate the effects of corilagin, an ellagitannin extracted from medicinal plants, on the frequency of seizures and cognitive function in a rat model of chronic epilepsy. MATERIAL AND METHODS Chronic epilepsy was induced in male Wistar rats by intraperitoneal (IP) injection of pentylenetetrazol (PTZ) for 36 days. Corilagin, 10 mg/kg and 20 mg/kg, was injected IP into treated rats, 24 days before the start of PTZ treatment, until the end of the protocol. The effects of corilagin were assessed by the pattern of epileptic seizures; cognitive function was assessed using the Morris water maze (MWM) navigation test. The mechanism of action of corilagin was investigated by measuring cytokine levels and oxidative stress parameters, including reactive oxygen species (ROS) production, and carbonic anhydrase inhibitory (CAI) activity. Histological analysis of fixed brain tissue sections included cresyl violet acetate staining (Nissl staining) for Nissl substance in the neuronal cytoplasm. RESULTS The corilagin-treated rats, compared with the control group, showed a significantly lower rate of epileptic events, improved cognitive function, reduced level of cytokines, reduced ROS production reduced CAI activity in the brain tissues (P<0.01). Histology of the rat brain tissues study showed that corilagin treatment maintained the neuronal cellular structure and number of surviving cells compared with the control group of rats. CONCLUSIONS The findings of this study showed that corilagin reduced the frequency of seizures and improved the cognitive function in a rat model of chronic epilepsy.

Atypical lower motor neuron disease with enlargement of Nissl substance: Report of an autopsy case.

The patient was an 81-year-old woman diagnosed with atypical motor neuron disease who died after a long clinical course (7.5 years without mechanical assistance of ventilation) characterized by lower motor neuron signs and symptoms. Upper motor neuron signs and cognitive impairment were not apparent. Autopsy demonstrated severe neuronal loss in the anterior horn of the spinal cord, and some of the remaining neurons showed enlargement of Nissl substance and apparent thickening of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures immunoreactive for phosphorylated transactivation response DNA-binding protein 43 were found. Immunoreactivity for superoxide dismutase-1 was focally seen in the enlarged Nissl substance. Ultrastructural examination demonstrated an increase of rough-surfaced endoplasmic reticulum (rough ER) and free ribosomes, disaggregation of polyribosomes, and dispersion of free ribosomes. Cisterns of rough ER were slightly dilated, and some of them were closely attached to the nuclear envelopes. Enlargement of Nissl substance may be related to "ER stress", and the abnormal findings of rough ER and free ribosomes may represent a degenerative process. However, another possibility, that they represent a compensatory hyperplastic change, cannot be excluded. The close attachment of cisterns of rough ER to the nuclear envelopes may be a mechanism to support or compensate for the abnormally-fragile nuclear envelopes.
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Pathophysiological changes in the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

In certain surgical procedures, sacrificing the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction, or hemorrhage that might occur after sectioning of the SPV. The present study investigated the pathophysiological changes in cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48, and 72 h groups which represented the time period from sacrificing of the SPV to killing of the rabbits. The water content (WC), Na+ content, K+ content, and pathophysiological changes in cerebellum and brain stem tissue were measured. In comparison with the control, the WC and Na+ content of cerebellar tissue were increased in the 4, 8, 12, and 24 h operation subgroups (P<0.05), but only increased in the 4-h subgroup of the brain stem tissue (P<0.05). The K+ content of the cerebellar tissue decreased in the 4, 8, 12, and 24 h operation subgroups (P<0.05) but only decreased in the 4-h subgroup of brain stem tissue (P<0.05). Nissl staining and TEM demonstrated that cerebellar edema occurred in the 4, 8, 12, and 24 h operation subgroups but not in the 48- and 72-h subgroups. Brain stem edema occurred in the 4-h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrificing of the SPV in the rabbit model.

Morphological and morphometrical maturation of ventral cochlear nucleus in human foetus.

Auditory impulses perceived by the hair cells of the organ of corti are relayed in the cochlear nucleus, the first relay station in the brainstem, by the cochlear nerve. The human foetus is well known to respond to sound during the last trimester of gestation. On the contrary, studies conducted in rat, cat and mouse have shown that these mammals have an immature auditory system at the time of birth. There are very few reports available regarding the morphological and functional maturation of the cochlear nucleus in human. Although the human cochlear nucleus neurons attain adult morphological characters by mid-gestation, there are hardly any studies discussing the functional maturation of the cochlear nucleus. Hence the present study was aimed at observing the morphological as well as functional maturation of the human foetal cochlear nuclei at various gestational ages. Morphological maturation was observed qualitatively while stereological estimation of the volume of well defined ventral cochlear nucleus (VCN) was calculated by the Cavalieri principle; neuronal count and density was estimated by dissector principle. The functional maturation was assessed by observing the expression of synaptophysin, a synaptic marker, at different gestational ages and by the presence of parvalbumin, a calcium binding functional neuronal marker by immunohistochemistry. Neurons showed coarse Nissl's substance and well developed cell processes and gradual increase in cell size by the 24th-30th gestational week. Synaptophysin labeling in the complete cochlear nucleus was observed at 20 weeks of gestation. Adult pattern of synaptophysin labeling was observed finally at37weeks of gestation. Earliest presence of parvalbumin expression was detected at 16 weeks of gestation and a distinct adult pattern was seen at 37 weeks of gestation. This study concluded that morphological and functional maturation of the human cochlear nuclei occurs simultaneously during mid-gestation which represents the critical period of development and continues up to term.

Neuroprotective effect of G14-humanin on global cerebral ischemia/reperfusion by activation of SOCS3 - STAT3 - MCL-1 signal transduction pathway in rats.

OBJECTIVE: Humanin (HN) has been identified to suppress neuron death. Gly14-HN (HNG), as a variant of HN, can decrease infarct volume after ischemia/reperfusion (I/R) injury. This study aimed to investigate the neuroprotective mechanism of HNG on global cerebral I/R (GI) in rats. METHODS: Rats were randomly divided into 13 groups: Sham group, GI groups and HNG groups. Both GI group and HNG groups included six time points (1, 3, 6, 12, 24, and 72 h). At 24 h after reperfusion, Nissl staining was used to observe positive neurons, and p-STAT3, MCL-1, SOCS3, Bax and Caspase-3 in different groups were detected by immunohistochemistry. qRT-PCR and western blot were used to evaluate the expression of STAT3, p-STAT3, MCL-1, and SOCS3. RESULTS: The immunohistochemistry also showed a significant increase in Bax (0.29 ± 0.007 vs. 0.22 ± 0.007, P < 0.01) and Caspase-3 (0.24 ± 0.02 vs. 0.18 ± 0.006, P < 0.01) in GI group compared with Sham group, while Bax (0.26 ± 0.01 vs. 0.29 ± 0.008, P < 0.01) and Caspase-3 (0.20 ± 0.008 vs. 0.24 ± 0.02, P < 0.01) were significantly decreased by HNG-treatment compared with GI group. Along with immunohistochemistry, western blot and qRT-PCR indicated that the protein and mRNA levels of STAT3, MCL-1, and SOCS3 were up-regulated after administration of HNG at six time points after global cerebral I/R in rat. CONCLUSION: HNG might exert neuroprotective effects through alleviating apoptosis and activating of SOCS3 - STAT3 - MCL-1 signal transduction pathway. Highlights (1) Cerebral ischemia led to neuronal loss in hippocampal CA1 region of rats. (2) HNG had neuroprotective effects on ischemia/reperfusion rats. (3) The protective effect of HNG might be related to the SOCS3 - STAT3 - MCL-1 pathway.