Shrunken Neurons Research Articles

Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson’s disease in mice

Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson’s disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1–7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by 1H and 13C nuclear magnetic resonance and ESI–MS spectral data. Compound 1 (6β,7β-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.

The presence of shrunken neurons with pyknotic nuclei in the dentate nucleus is a common postmortem change associated with autolysis of the cerebellar granular cell layer.

The presence of shrunken neurons with pyknotic nuclei in the dentate nucleus is a common postmortem change associated with autolysis of the cerebellar granular cell layer.

Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke.

Ischemic stroke is the second-leading cause of death. Hyperglycemia, which is characteristic of diabetes mellitus, contributes to the development of endothelial dysfunction and increases the risk of stroke. Isoxsuprine is an efficient beta-adrenergic agonist that improves blood flow to the ischemic aria and stops the infarct core from growing. However, low bioavailability, a short biological half-life, and first-pass hepatic metabolism reduce the therapeutic efficacy of oral isoxsuprine. Therefore, the authors focused on developing isoxsuprine-loaded liposomes containing ethanol and propylene glycol (ILEP) formulation as nasal drops for the treatment of ischemic stroke in diabetic patients. Different ILEP formulations were optimized using Design Expert software, and the selected formulation was examined in vivo for its anti-stroke effect using a rat model of diabetes and stroke. The optimized ILEP, composed of 15% propylene glycol, 0.16% cholesterol, 10% ethanol, and 3.29% phospholipid, improved the sustainability, permeation, and targeting of isoxsuprine. Furthermore, the in vivo studies verified the improved neurological behavior and decreased dead shrunken neurons and vascular congestion of the rats treated with the optimized ILEP formulation, demonstrating its anti-stroke activity. In conclusion, our study found that treatment with an optimized ILEP formulation prevented the initiation and severity of stroke, especially in diabetic patients.

Apitoxin alleviates methyl mercury-induced peripheral neurotoxicity in male rats by regulating dorsal root ganglia neuronal degeneration and oxidative stress

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats.

Morphological changes in the neurons of the parietal cortex and hippocampus of rats with subtotal cerebral ischemia under conditions of the use of modulators of the L-arginine-NO pathway and against the background of the administration of Omega-3 pol

Cerebrovascular diseases of ischemic genesis tend to increase, rejuvenate, are associated with severe clinical course, high rates of disability and mortality. The urgency of the problem of cerebrovascular diseases can rightfully be defined as extraordinary, requiring the concentration of efforts of specialists of different profiles to solve it. Subtotal cerebral ischemia leads to the development of morpho functional disturbances of the cerebral cortex. The introduction of Omega-3 polyunsaturated fatty acids has a corrective effect on the hippocampus in conditions of subtotal ischemia, reducing the number of shadow cells and hyperchromic shrunken neurons, without significantly affecting the size and shape of neurons in the cerebral cortex. Prior administration of L-NAME, the use of Omega-3 did not prevent the effects of the NO synthase inhibitor and associated NO deficiency at this dose and route of administration.

Using L-Arginine-No Pathway Modulators in Rats with Subtotal Cerebral Ischemia. Histological Changes

Acute cerebrovascular accident is one of the most urgent problems in modern medicine. The frequency of strokes varies in different regions of the world from 1 to 4 cases per 1000 population per year, increasing significantly with age. Cerebrovascular diseases of ischemic origin tend to grow, rejuvenate, are associated with a severe clinical course, high rates of disability and mortality [1-6]. The relevance of the problem of cerebrovascular diseases can rightfully be defined as extraordinary, requiring the concentration of efforts of specialists of different profiles to solve it. Subtotal cerebral ischemia leads to the development of morphological and functional disorders of the cerebral cortex. The introduction of a non-selective NO–synthase inhibitor - L-NAME aggravated histological disorders of neurons that occur with SCI: an increase in the number of hyperchromic shrunken neurons, a decrease in the size and deformation of their pericaryons. Additional use of L -arginine partially eliminated the negative effect of L – NAME [1-8].

The neuroprotective effect of ginsenoside Rb1 on the cerebral cortex changes induced by aluminium chloride in a mouse model of Alzheimer's disease: A histological, immunohistochemical, and biochemical study

Alzheimer's disease (AD) is one of the most common types of dementia among neurodegenerative disorders characterized by attention deficits and memory loss. Panax ginseng is a traditional Chinese herbal remedy that has been employed for millennia to manage dementia linked with aging and memory impairment. Ginsenoside Rb1 is one of Panax ginseng's most abundant components. The present work evaluated the neuroprotective effects of ginsenoside Rb1 on the cerebral cortex of AlCl3-induced AD in adult male albino mice. Forty male mice were alienated arbitrarily into; control group, ginsenoside Rb1 group (70 mg/kg/day), AlCl3 group (50 mg/kg/day), and ginsenoside Rb1-AlCl3 group that received ginsenoside Rb1 one hour before AlCl3. Oxidative stress parameters, Amyloid β (Aβ) and phosphorylated tau protein, and acetylcholine esterase (AChE) activity were measured. Cerebral cortex sections were evaluated histologically by light microscopic examination and immunohistochemistry. AlCl3-induced memory impairment, Aβ and phosphorylated tau protein accumulation, and AChE elevation. Moreover, histopathological alterations in the cerebral cortex were reported in the form of irregular shrunken neurons and the surrounding neuropil showed vacuolation. Some neurons appeared with darkly stained nuclei, others had faintly stained ones. The synaptophysin expression was significantly decreased, while the expression of cleaved caspase-3, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were significantly elevated. It's interesting to note that these changes were attenuated in mice pretreated with ginsenoside Rb1. Collected data indicated that ginsenoside Rb1 showed a potential neuroprotective effect against cerebral cortex changes caused by AlCl3 via suppression of Amyloid β and phosphorylated tau protein formation, oxidative stress correction, anti-apoptotic effect, and by minimizing gliosis.

Three-dimensional structure of the facial canal and related blood vessels and nerves in the temporal bone.

There are only limited anatomical data on nerves, veins, and arteries in the temporal bone. More detailed anatomical data are required to improve planning of treatments targeting the temporal bone region. Herein, we performed a detailed analysis of the facial canal (FC) and the related carotid artery and vein. We examined the bony structure of the middle ear and FC, jugular foramen, and carotid canal in 30 Japanese elderly donor cadavers. Three-dimensional reconstruction of the canal structure was achieved using cone beam computed tomography, while macroscopic and histological analyses were also performed. The FC form was classified as either straight (28%) or bent (72%). There were significant differences in the diameter of the FC and the distance between the internal jugular vein, other FC branches, and the FC. Principal component analysis (PCA) was performed for the FC using 29 factors. Two principal components significantly explained 30.9% (component 1, 18.6%; component 2, 12.3%) of the FC. Histological observation showed numerous ganglion cells and shrunken neurons in the geniculate ganglion of the facial nerve of elderly samples. FC diameter is an important contributor to the relationship between the FC and the jugular foramen. The FC and the internal jugular vein are located close to each other, which is useful information for the trans-canal surgery of the otology. Furthermore, the geniculate ganglion contains numerous ganglion cells and shrunken neurons, which may affect the FC structure during bone matrix remodeling with aging.

Protective effects of evening primrose oil on behavioral activities, nigral microglia and histopathological changes in a rat model of rotenone-induced parkinsonism

Parkinson’s disease (PD) is a neurodegenerative illness described as damage to dopaminergic neurons. There is increasing evidence that neuroinflammatory activity mediated by microglia is extensively involved in the initiation and development of PD. This study assessed the protective effect of evening primrose oil [EPO] as an anti-inflammatory mediator in rotenone-induced Parkinsonism in rats. Forty-eight adult male albino rats were distributed into four groups. Group I: control. Group II: rotenone [1.5 mg/kg/48 h] was administered subcutaneously to the rats. Groups III and IV: the rats had rotenone plus daily oral [EPO] 5 and 10 mg/kg respectively. After 24 days, motor behaviour was assessed by the open field and rotarod tests. The brain striata were isolated and tested for tumor necrosis factor (TNF)-α, interleukin 6, NF-B [nuclear factor-kappa B], and dopamine levels. The mid-brain tissues were processed for light and electron microscopy examinations, and immunohistochemical staining for tyrosine hydroxylase [TH], and microglia cells' markers: [CD68 and IBA1]. Results revealed that rotenone-treated rats had poor motor function, a significantly increased striatal level of inflammatory markers, markedly shrunken neurons, degeneration, pyknotic neuroglia, neuropil vacuolation, markedly destructed swollen mitochondria with loss of their cristae, and dilated rough endoplasmic reticulum, as well as decreased TH and increased CD68 and IBA1-positive cells. Treatment with EPO ameliorates all the neuropathological changes of rotenone in the rat brain. In conclusion, EPO enhanced the motor performance, reduced the inflammatory marker levels, restored dopamine levels, and ameliorated the neurohistopathological lesions of rats with experimental parkinsonism, suggesting its neuroprotective and anti-inflammatory effects.

Serum and brain metabolomic study reveals the protective effects of Bai-Mi-Decoction on rats with ischemic stroke.

Bai-Mi-Decoction (BMD), which is composed of Eugenia caryophyllata, Myristica fragrans, Moschus berezovskii, and Crocus sativu, is a characteristic TCM multi-herb formula for brain disease. However, the mechanism of protective effects of BMD on ischemic stroke (IS) still has not been clarified. Our study is designed to elucidate the protective effects and underlying mechanisms of BMD on IS by employing pharmacodynamic and serum and brain metabolomic methods. In this experiment, 90 adult male Sprague-Dawley rats were randomly divided into the sham operation group (SHAM, vehicle), middle cerebral artery occlusion-reperfusion injury model group (MCAO/R, vehicle), positive control group (NMDP, 36mg/kg/day nimodipine), and low (BMDL, 0.805g/kg/day), moderate (BMDM, 1.61g/kg/day), and high (BMDH, 3.22g/kg/day) dosage of BMD prophylactic administration groups. The drugs were dissolved in 0.5% CMC-Na and orally administered to rats with equal volumes (100g/ml body weight) once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, change in body weight, and serum NO, SOD, MDA, GSH, and GSSG levels were determined. Pathological abnormalities using hematoxylin and eosin staining and the expression of VEGF, caspase-3, and NF-κB were analyzed. Furthermore, serum and brain metabolic profiles were explored to reveal the underlying mechanism using UHPLC-QTOF-MS/MS technology. BMD exhibited significant neuroprotective effects on MCAO/R rats. As compared to the MCAO/R model group, it could reduce the neurological deficit score and cerebral infarct volume, increase body weight, enhance GSH, SOD, and GSSG activities, and decrease NO and MDA contents of MCAO/R rats. Meanwhile, BMD could ameliorate pathological abnormalities of MCAO/R rats through reducing neuronal loss, vacuolated spaces, shrunken neurons, and destructed neuron structure, as well as regulating the expression of VEGF, caspase-3, and NF-κB. UHPLC-QTOF-MS/MS-based serum and brain metabolomics analysis found a total of 53 differential metabolites between MCAO/R and SHAM groups, of which 30 were significantly regulated by BMD intervention, and further metabolic pathway analysis implied that the protective effects were mainly associated with amino acid and glycerophospholipid metabolisms. Our pharmacodynamic and metabolomic results revealed the neuroprotective effects of BMD on MCAO/R rats, and the underlying mechanisms were probably related to amino acid and glycerophospholipid metabolisms.

Structural and Functional Reorganization of the Sensorimotor Cortex During Ligation of the Common Carotid Arteries (Experimental Study)

Aim of the study. To explore the structural and functional changes of neurons, glial cells, and synaptic terminals in layers I, III, and V of the sensorimotor cortex (SMC) of the rat brain after bilateral common carotid artery ligation (CCAL).Material and methods. Incomplete cerebral ischemia was simulated by irreversible bilateral CCAL (2-vessel model of global ischemia without hypotension) on white rats (n=36). Comparative evaluation of the studied SMC structures was performed in the control group (intact rats, n=6) on days 1, 3, 7, 14, and 30 (n=30) after CCAL. Nissl, hematoxylin-eosin staining, and immunohistochemical reactions for NSE, MAP-2, p38, GFAP, and IBA1 were used. Numerical density of pyramidal neurons, astrocytes, oligodendrocytes, microglial cells, and relative area of p38-positive material (synaptic terminals) were determined. Statistical hypotheses were tested using nonparametric methods with Statistica 8.0 software.Results. After CCAL, the number of degenerative neurons in rat brain SMCs increased. The peak of numerical density of unshrunken neurons was detected after day 1. Later, the numerical density of hyperchromic unshrunken neurons decreased, while that of shrunken neurons increased. These parameters did not reach the control values. The changes in SMC neurons were accompanied by an increase in the numerical density of microglial cells after day 1 and its subsequent decrease. Immunohistochemistry for IBA1 revealed signs of microglial cell activation such as change in shape and loss of processes. Maximum increase in the SMC density of oligodendrocytes was observed on day 7, and that of astrocytes on day 14 after CCAL. The maximum number of NSE-positive neurons occurred on day 1 after CCAL. There was a significant decrease in the number of NSEpositive neurons in SMC layer III on days 3, 7, and 14, and an increase in the number of NSE-positive neurons on day 30. The number of NSE-positive neurons in layer V of the SMC progressively decreased throughout the whole study period. The evolution of changes in the proportion of p38-positive material (synaptic terminal area) differed significantly between the layers of SMC. In the layers I and III, this parameter first decreased (days 1 and 3) and then increased (days 7, 14, and 30). In layer V of SMC, the activation of the protein expression was observed in the acute phase (days 1 and 3), then it decreased on days 7 and 14, and increased again on day 30. The changes found in the numerical density of neurons, glial cells and synaptic terminals were associated with dehydration and overhydration of SMC. We found strong to medium significant associations between the relative area of terminals and neuropil swelling and edema zones.Conclusion. After CCAL, layers I, III, and V of the SMC of white rats revealed destructive and compensatory changes in neurons, glial cells, and inter-neuronal communication structures. Taken together, all these changes indicate a significant layer-by-layer variability of the neural tissue response to CCAL. Layer III (secondary projection complex) of the SMC was affected to a greater extent. Reorganization of neuronal-glial and interneuronal interrelations occurred along with a prominent neuropil overhydration.

Changes in respiration of the mitochondrial fraction of brain homogenates in rats with stepwise incomplete cerebral ischemia

Objective: to conduct a comparative analysis of mitochondrial respiration in brain homogenates of rats with stepwise incomplete cerebral ischemia (SICI) with varying duration between ligations of both common carotid arteries (CCA). Material and methods. The experiments were performed on 24 male mongrel white rats weighing 260±20 g. All rats were distributed among three subgroups. Cerebral ischemia was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group (n=6) comprised sham-operated rats of similar gender and weight. To study mitochondrial respiration, the brain was extracted in the cold environment (0-4 °C), dried with filter paper, weighed and homogenized sensu the modified technique in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH of 7.4 (in a ratio of 1:10), using Potter – Elvehjem homogenizer with Teflon pestle. Results. SICI with an interval of 1 and 3 days between ligation of both CCA led to neuronal damage in the parietal cortex and hippocampus of rats, which manifested itself in a reduction of the neuron size, deformation of the perikaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with one-day interval between ligations. These changes were similar to the changes in incomplete cerebral ischemia (ICI) (p=0.07), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of those in the parietal cortex. ICI with seven-day interval between ССА ligations, on the contrary, was manifested by less pronounced histological changes, especially in the hippocampus. Conclusion. Comparative analysis of mitochondrial respiration in brain homogenates revealed that the severity of brain damage in SSIC depended on the interval between blood flow arrest in both CCA. At the same time, the highest level of energy metabolism disorder was observed during CCA ligation with an interval of one day, which implied insufficient implementation of compensatory mechanisms.

Effect of <i>Ginkgo biloba</i> extract on Histomorphometric changes of Hippocampus against Fluoride Toxicity in Wistar Rats

Prolonged ingestion of fluoride leads to the pathogenesis known as fluorosis. Fluoride exposure leads to neuro degenerative changes such as reduction in the neuronal cell size and number. Exposure to fluoride showed neurodegenerative changes like shrunken neurons, increased in folding of the nuclear membrane, mitochondrial alterations, and dilated rough endoplasmic reticulum cisternae and clusters of vesicles near the Golgi bodies. Present study is to explore the histomorphometric changes of the hippocampus of fluoride induced brain and treated with Ginkgo biloba Extract (GBE). Thirty number (30) adult male Wistar rats were randomly separated into 5 Groups (n=6). Group1 (Control) supplemented with water, 2 to 5 Groups were supplemented with 100ppm of sodium fluoride for 30 days, while the Groups 3, 4, and 5 were Ginkgo biloba extract treated at 50mg/ kg, 100mg/kg and 200mg/kg body weight for 15 days, after sodium fluoride treatment, results showed that, 200mg/kg GBE provided effective and complete protection against fluoride toxicity. From the present study concluded that 50, 100 and 200 mg/kg GBE was significantly attenuated the fluoride induced toxicity in a dose depending manner. Present histomorphometrical study showed delayed neuronal death in the CA1 and CA3 regions of hippocampus of fluoride group that was significantly attenuated by GBE (50,100 and 200 mg/kg) in a dose dependant manner.

Stepwise Cerebral Ischemia Causes Disturbances in Mitochondrial Respiration of Neurons in the Cerebral Cortex of Rats

Objectives: To conduct a comparative analysis of respiration of mitochondria of brain homogenates of rats with stepwise subtotal cerebral ischemia with different duration between ligations of both common carotid arteries. Methods: The experiments were performed on 24 male mongrel white rats weighing 260 ±20 g. Cerebral ischemia (CI) was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group consisted of falsely operated rats of similar sex and weight. To study mitochondrial respiration, the brain was extracted in the cold (0-4°C), dried with filter paper, weighed and homogenized in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4 (in a ratio of 1:10), using Potter-Evelheim homogenizer with Teflon pestle according to the modified method. To prevent systematic measurement errors, brain samples from the compared control and experimental groups of animals were studied under the same conditions. Results: Stepwise SCI with an interval of 1 and 3 days between bandages of both OCA leads to damage to the neurons of the parietal cortex and hippocampus of rats, which manifests itself in a decrease in their size, deformation of the pericaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with an interval between dressings of 1 day. These changes were similar to the changes in SCI (p>0.05), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of them in the parietal cortex. SCI with an interval between WASP dressings of 7 days, on the contrary, it is manifested by less pronounced histological changes, especially in the hippocampus. Conclusion: In cerebral ischemia, damage to the inner mitochondrial membrane occurs due to activation of free radical oxidation processes. Damage to the inner mitochondrial membrane, in turn, leads to an increase in its permeability and a decrease in the level of the proton gradient due to the transition of protons along the concentration gradient through the resulting nonspecific pores into the mitochondrial matrix. As a result, the efficiency of ATP synthesis decreases, and more substrates and oxygen are required to maintain the intermembrane potential under these conditions.

Interrelation structural and functional alterations in the dentate gyrus of rats with aging.

The process of natural aging is considered as a risk factor for the development of neurodegenerative pathology, in which decrease of physiological cognitive functions of the body is found. 2 groups were formed: group 1 - rats at the age of 12 months (n = 10), group 2 - rats at the age of 24 months (n = 10). We evaluated the neuropsychiatric state of animals and determined the degree injury of neurons. It was established that the motor and orientational-research activity of old rats (24 months) was lower than that of rats of mature age (12 months). Microscopic examination of rat brain sections stained with thionin according to the Nissl method in mature animals in the granular layer of dentate gyrus showed that the most of neuronal perikarya had a close to round shape with a centrally located nucleus and nucleolus, characterized by normochromic cytoplasm and compact arrangement. There were single neurons with hyperchromatosis of the cytoplasm and wrinkled hyperchromic neurons, which were mainly located on the border of granular and subgranular layers of dentate gyrus. Sites of neuronal loss were observed in senile age rats, a significant increase in both the specific number of hyperchromic shrunken neurons (p <0.05) and neurons with cytoplasm hyperchromatosis without shrinkage (p <0.05) was observed. Such neurons prevailed at the boundary of the granular and subgranular layers, as well as in the crest region. During aging in rats aged 24 months, pronounced changes in neurons of granular layer of dentate gyrus in the form of an increase in the number of hyperchromic shrunken neurons are found at the boundary of granular and subgranular layers and in the crest region. These changes are accompanied by more severe functional disorders in 24-month-old rats which may accelerate the process of aging.

Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging.

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

Growth Performance and Clinicopathological Analyses in Lambs Repetitively Inoculated with Aluminum-Hydroxide Containing Vaccines or Aluminum-Hydroxide Only

Simple SummaryAluminum-hydroxide is an effective vaccine adjuvant used in most commercial sheep vaccines. It facilitates the establishment of a robust immune response against the vaccine antigen. During the first decade of the 21st century, repetitive injections with vaccines containing aluminum-based adjuvants were proposed to be linked to a progressive wasting syndrome in sheep. The aim of this work was to analyze several clinicopathological parameters, including growth performance, clinical data, and histopathological observations in lambs intensively injected with aluminum-containing vaccines, aluminum-hydroxide only, or a saline solution as control. Although aluminum-hydroxide was linked to chronic inflammatory reactions at the injection site and the development of behavioral changes in sheep, the results presented here indicate that injected aluminum-hydroxide, either alone or in combination with vaccine antigens, is not enough to induce relevant changes in the parameters studied. Other factors such as sex, breed, age, production system, diet or climate conditions could play a role in the development of the previously described wasting syndrome.Aluminum (Al) hydroxide is an effective adjuvant used in sheep vaccines. However, Al-adjuvants have been implicated as potential contributors to a severe wasting syndrome in sheep—the so-called ovine autoimmune-inflammatory syndrome induced by adjuvants (ASIA syndrome). This work aimed to characterize the effects of the repetitive injection of Al-hydroxide containing products in lambs. Four flocks (Flocks 1–4; n = 21 each) kept under different conditions were studied. Three groups of seven lambs (Vaccine, Adjuvant-only, and Control) were established in each flock. Mild differences in average daily gain and fattening index were observed, indicating a reduced growth performance in Vaccine groups, likely related to short-term episodes of pyrexia and decreased daily intake. Clinical and hematological parameters remained within normal limits. Histology showed no significant differences between groups, although there was a tendency to present a higher frequency of hyperchromatic, shrunken neurons in the lumbar spinal cord in the Adjuvant-only group. Although Al-hydroxide was linked to granulomas at the injection site and behavioral changes in sheep, the results of the present experimental work indicate that injected Al-hydroxide is not enough to fully reproduce the wasting presentation of the ASIA syndrome. Other factors such as sex, breed, age, production system, diet or climate conditions could play a role.

Neuroprotective Effect of Chrysin in Rat Model of Parkinsons Disease: Histopathological Evidence

Parkinson’s disease (PD) is a neurodegenerative ailment that worsens over time. PD is characterized by severe motor and non-motor symptoms. Because there is no cure for Parkinson's disease, current treatments heavily rely on relieving symptoms. The current research explores the histopathological changes in the different brain regions including the cerebral cortex, hippocampus, and striatum after subcutaneous rotenone administration every other day for 21 days in adult male Wistar rats. Substantial morphological changes were noticed in cell area. Sections examined showed severe neuronal loss and excessive appearance of abnormal damaged, shrunken red neurons, intercellular edema and vacuolation of intercellular neuropile and loss of myelinated fibers. After the last rotenone injection, chrysin and L-dopa were given for 28 days. The findings showed that chrysin treatment displayed significant improvement in the neuronal architecture and decrease of damage caused by rotenone in different brain regions. This appeared in the form of moderate protective efficacy with the persistence of loss in normal neuronal densities. However, combined treatment of rotenone-injected animals with chrysin and L-dopa was associated with more records of visible intact neurons and fewer records of abnormal degenerative changes in various brain neuronal areas This study concludes that chrysin may be a useful drug alone or with L-dopa for the treatment of rotenone-induced PD.

Protective effect of methylene blue against copper oxide nanoparticle-induced neurobehavioral toxicity

Increasing attention has been paid in the past decade to assessing the toxicological effects of nanoparticles and finding a protectant; thus, the current study aimed to investigate the protective effect of the mitochondria-targeting drug methylene blue (MB) against copper oxide nanoparticle (CuO-NP)-induced neurobehavioral toxicity in rats. For this purpose, twenty rats were allocated to four equal groups (n = 5). The negative control group received distilled water intraperitoneally (IP) and Tween 80 (10 %) orally. The CuO-NP group was given a dose of 100 mg/kg of CuO-NPs, administered orally, and the positive control group was treated with 1 mg/kg MB intraperitoneally (IP). The final group was concurrently exposed to CuO-NPs and MB for 14 consecutive days. At the end of the study, each group was neurobehaviorally blind tested relative to other experimental animals, then brain tissue markers were determined and a histopathological examination was conducted. The results showed that supplementation with CuO-NPs induced neurobehavioral alterations; increased Cu content in the brain; and enhanced lipid peroxidation (malondialdehyde [MDA]), protein peroxidation (protein carbonyl [PC]), and DNA oxidative damage (8-hydroxy-2-deoxyguanosine [8−OH-dG]) compared to other treatments. In addition, a decrease was noted in the mitochondrial dehydrogenases’ (aldehyde dehydrogenase 2 [ALDH2], and glutamate dehydrogenase [GDH]) activity in Cu-exposed rats. The histopathological findings revealed shrunken, pyknotic, and hypereosinophic cortical neurons and increased immune positive brown staining of caspase-3 protein, indicating apoptosis. Co-treatment with methylene blue ameliorated the neurotoxic effects of CuO-NPs; therefore, MB evidently had a powerful modulatory effect against the neurotoxicity of nano-Cu oxide via its antioxidant and mitochondrial protection properties.

Decrease of 14\u20133-3 proteins by glutamate exposure in the cerebral cortex of newborn rats

Glutamate is a representative excitatory neurotransmitter. However, excessive glutamate exposure causes neuronal cell damage by generating neuronal excitotoxicity. Excitotoxicity in neonates caused by glutamate treatment induces neurological deficits in adults. The 14–3-3 family proteins are conserved proteins that are expressed ubiquitously in a variety of tissues. These proteins contribute to cellular processes, including signal transduction, protein synthesis, and cell cycle control. We proposed that glutamate induces neuronal cell damage by regulating 14–3-3 protein expression in newborn animals. In this study, we investigated the histopathological changes and 14–3-3 proteins expressions as a result of glutamate exposure in the neonatal cerebral cortex. Rat pups at post-natal day 7 were intraperitoneally administrated with vehicle or glutamate (10 mg/kg). Animals were sacrificed 4 h after treatment, and brain tissues were fixed for histological study. Cerebral cortices were isolated and frozen for proteomic study. We observed serious histopathological damages including shrunken dendrites and atypical neurons in glutamate-treated cerebral cortices. In addition, we identified that 14–3-3 family proteins decreased in glutamate-exposed cerebral cortices using a proteomic approach. Moreover, Western blot analysis provided results that glutamate treatment in neonates decreased 14–3-3 family proteins expressions, including the β/α, ζ/δ, γ, ε, τ, and η isoforms. 14–3-3 proteins are involved in signal transduction, metabolism, and anti-apoptotic functions. Thus, our findings suggest that glutamate induces neonatal neuronal cell damage by modulating 14–3-3 protein expression.