Predetermining glenoid dimensions using the scapular dimensions.

BACKGROUND: Variations of morphology of the glenoid cavity have been previously reported. These influence the surgical reconstruction or arthroplasty of the shoulder. This study aims to study the variation of the shape of suprascapular notch, shape of glenoid cavity, dimensions of both the scapular and the glenoid cavity, and predict the glenoid dimensions from the scapular dimension parameters. MATERIALS AND METHODS: Adult-dried scapulae were collected. The shapes of each suprascapular notch and glenoid cavity were evaluated. The scapular height, scapular width, glenoid superoinferior distance, and glenoid anteroposterior distance were measured using a digital vernier caliper, and statistical analysis was conducted on the data that were obtained. RESULTS: There were 264 scapulae included in this study (166 male and 98 female). Most of the glenoid cavities were pear shaped (69.7%). The two most common types of suprascapular notches were small depression notches (31.8%) and the absence of notches (25.8%). The mean ± SD of scapular height, scapular width, glenoid superoinferior distance, and glenoid anteroposterior distance were 148.2 ± 10.0, 108.1 ± 6.4, 37.1 ± 2.2, and 27.4 ± 2.1 mm, respectively, in the male samples and 133.0 ± 7.0, 97.0 ± 5.2, 33.2 ± 1.9, and 23.7 ± 1.7 mm, respectively, in the female samples. The male scapulae were significantly larger than the female scapulae (p value < 0.05). However, there were no differences between the male and female scapulae in terms of scapular index or glenoid index (p value > 0.05). Scapular height and width were significantly associated with both the glenoid superoinferior distance (p = 0.0001) and glenoid anteroposterior distance (p value = 0.0001). CONCLUSION: Scapular height and width can predict the dimensions of the glenoid. In cases of glenoid bone loss or shoulder arthroplasty, the native normal glenoid dimensions can be determined from the scapular dimensions as visualized using a true scapular anteroposterior radiograph. The surgeon can use these preoperative parameters when performing glenoid reconstruction or shoulder arthroplasty.

Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension.

A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities.

Localization of the cystogenous glands of Opisthorchis viverrini cercariae.

Opisthorchiasis in northeastern Thailand is an important etiology of cholangiocarcinoma. To form the infectious stage, free swimming cercariae penetrate cyprinid fish, shed their tails, and then secret a cystic substance to cover their larval stage to form metacercariae in the fish body. We determined the location of the cystogenous glands in Opisthorchis viverrini cercariae. The cercariae and metacercariae were obtained from the naturally infected snail host, Bithynia siamensis goniomphalos and from cyprinid fish, respectively. The cyst walls of the metacercariae were separated and used to immunize inbred male BALB/c mice to obtain cyst wall antibodies. The general characteristics of the O. viverrini cercariae and metacercariae were studied by hematoxylin and eosin (H&E) staining of sections. The location and ultrastructure of the cystogenous glands of cercariae were studied by immunoperoxidase, immunofluorescence and transmission electron microscopy. The structures and organelles of cercariae and metacercariae could be identified, but the cystogenous glands could not be detected in H&E sections. The immunoperoxidase and immunofluorescence sections revealed positive reactions for cystogenous glands predominanted in the lateral part of the cercariae and were clearly seen in the cyst wall of the metacercariae. The ultrastructure of the cystogenous glands contained semitranslucent electron dense oval shaped granules. If interference occurs during the formation of the cysts by fish immune response, the metacercariae may not develop to maturity. It may be easily digested or degraded by human stomach acid and pepsin. This may be an efficient method for control of O. viverrini infection which requires further detailed study.

Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model.

l-methionine (L-met) is a substantial non-polar amino acid for normal development. L-met is converted to homocysteine that leads to hyperhomocysteinemia and subsequent excessive homocysteine in serum resulting in stimulating oxidative stress and vascular dementia. Several studies have found that hyperhomocysteine causes neuronal cell damage, which leads to memory impairment. Caffeic acid is a substrate in phenolic compound discovered in plant biosynthesis. Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances GSH and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. Hence, we investigated the protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-met in rats. Six groups of Sprague Dawley rats were assigned including control, L-met (1.7 g/kg/day), caffeic acid (20, 40 mg/kg), and L-met + caffeic acid (20, 40 mg/kg) groups. Spatial and recognition memories were subsequently examined using novel object location (NOL) and novel object recognition (NOR) tests. Moreover, the immunofluorescence technique was performed to detect Ki-67/RECA-1, bromodeoxyuridine (BrdU)/NeuN and p21 markers to represent hippocampal neurogenesis changes. The results revealed decreases in vasculature related cell proliferation and neuronal cell survival. By contrast, cell cycle arrest was increased in the L-met group. These results showed the association of the spatial and recognition memory impairments. However, the deterioration can be restored by co-administration with caffeic acid.

Curcumin prevents bile canalicular alterations in the liver of hamsters infected with Opisthorchis viverrini.

Opisthorchis viverrini infection causes inflammation and liver injury leading to periductal fibrosis. Little is known about the pathological alterations in bile canaliculi in opisthorchiasis. This study aimed to investigate bile canalicular alterations in O. viverrini-infected hamsters and to examine the chemopreventive effects of curcumin on such changes. Hamsters were infected with O. viverrini and one group of animals was fed with 1% dietary curcumin supplement. Animals were examined during the acute infection phase, days 21 and 30 post-infection (PI) and chronic infection phase (day 90 PI). Scanning electron microscopy revealed that in the infected group fed with a normal diet, bile canaliculi became slightly tortuous by 30 day PI and more tortuous at day 90 PI. Transmission electron microscopy showed a reduction in microvilli density of canaliculi starting at day 30 PI, with a marked loss of microvilli at day 90 PI. These ultrastructral changes were slightly seen at day 21 PI, which was similar to that found in infected animals fed with 1% curcumin-supplemented diet. Notably, curcumin treatment prevented the reduction of microvilli density, reduced the dilation of bile canaliculi, and decreased the tortuosity of the bile canaliculi relative to non-infected animals on a normal diet at days 30 and 90 PI. These results suggest that curcumin reduces alteration of bile canaliculi and may be a promising agent to prevent the onset of bile duct abnormalities induced by O. viverrini infection.

Protective effect of metformin on methotrexate induced reduction of rat hippocampal neural stem cells and neurogenesis.

Adult neurogenesis is a process in which the adult neural stem cells produce newborn neurons that are implicated in terms of learning and memory. Methotrexate (MTX) is a chemotherapeutic drug, which has a negative effect on memory and hippocampal neurogenesis in animal models. Metformin is an antidiabetic drug with strong antioxidant capacities. We found that metformin ameliorates MTX induced deteriorations of memory and hippocampal neurogenesis in adult rats. In this study, we focus to investigate neural stem cells, biomarkers of apoptosis, and the protein for synaptogenesis, which involves in the transcription factors of the hippocampus in rats that received metformin and MTX. Male Sprague-Dawley rats were composed of control, MTX, metformin, and MTX+metformin groups. MTX (75 mg/kg, i.v.) was given on days 7 and 14, whereas metformin (200 mg/kg, i.p.) was given for 14 days. Hippocampal neural stem cells in the subgranular zone (SGZ) were quantified using immunofluorescence staining of Sox2 and nestin. Protein expression including PSD95, Casepase-3, Bax, Bcl-2, CREB, and pCREB were determined using Western blotting. MTX-treated rats displayed decreases in Sox2 and nestin-positive cells in the SGZ. Increases in Caspase-3 and Bax levels and decreases in PSD95, Bcl-2, CREB, and pCREB protein expressions in the hippocampus were also detected. However, these negative impacts of MTX were ameliorated by co-treatment with metformin. These consequences postulate that metformin has a potential to increase neural stem cells, synaptic plasticity, decreased apoptotic activities, and transcription factors, resulting in upregulation of hippocampal neurogenesis in MTX-treated rats.

Hesperidin ameliorates impairment in hippocampal neural stem cells related to apoptosis induced by methotrexate in adult rats.

Neurogenesis is a process of generating neural stem cells (NSCs) as functional neurons can be decreased after chemotherapy treatments. Methotrexate (MTX) is a folate antagonist that is used for cancer treatment but has negative effects, including oxidative stress, neuronal apoptosis and cognitive impairments. Hesperidin (Hsd), a flavonoid found in citrus fruits, has antioxidant and neuroprotection properties. This study investigated whether Hsd could attenuate impairments of hippocampal neural stem cells related to apoptosis induced by MTX. Spraque-Dawley rats (n = 24) were divided into 4 groups: (1) Vehicle group received propylene glycol (21 days) and 0.9% normal saline (day 8 and 15), (2) Hsd group received 100 mg/kg (21 days), (3) MTX group received 75 mg/kg (days 8 and 15) and (4) MTX+Hsd group received MTX, 75 mg/kg (day 8 and 15) and Hsd 100 mg/kg (21 days). Our results showed that MTX decreased hippocampal neural stem cells including SRY (sex determining region Y)-box 2 (SOX2) and nestin. MTX diminished vascular related (VR) Ki-67 positive cells in the hippocampus but not non-vascular related (NVR) Ki-67. Additionally, MTX reduced SOX2, nestin, postsynaptic density protein 95 (PSD-95) and B-cell lymphoma-2 family of proteins (Bcl-2), whereas Bax and caspase-3 were enhanced in the hippocampal tissues. Interestingly, co-treatment with Hsd and MTX revealed upregulation of SOX2, nestin and VR Ki-67 positive cells as well as elevated SOX2, nestin, PSD-95 and Bcl-2 proteins. Moreover, receiving both Hsd and MTX significantly suppressed increased Bax and caspase-3. These results confirm that Hsd can ameliorate MTX-induced impairments of hippocampal NSC proliferation and neuronal apoptosis.

Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aß1-42-induced rats.

BACKGROUND: Alzheimer's disease (AD) pathogenesis is associated with amyloid-ß (Aß)-induced neuroinflammation. In AD, the activation of microglia caused by Aß accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models. OBJECTIVES: This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aß1-42 protein levels, and neuroinflammation in Aß1-42-induced rats. METHODS: Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aß, CB + Aß CHRE125 + Aß, CHRE250 + Aß, and CHRE500 + Aß. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aß1-42 at a concentration of 1 µg/µl were injected into both lateral ventricles (1 µl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aß1-42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1ß, and TNFα) were investigated in the cerebral cortex and hippocampus. RESULTS: Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aß1-42 protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex. CONCLUSIONS: This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aß1-42 protein levels and neuroinflammation caused by Aß1-42.

Neuroprotective properties of chrysin on decreases of cell proliferation, immature neurons and neuronal cell survival in the hippocampal dentate gyrus associated with cognition induced by methotrexate.

Methotrexate (MTX) is a drug widely used for chemotherapy and can reduce cancer cell production by inhibiting dihydrofolate reductase and decreasing cancer cell growth. MTX has a neurotoxic effect on neural stem and glial cells, leading to memory deficits. Chrysin is a natural flavonoid that contains essential biological activities, such as neuroprotective and cognitive-improving properties. Therefore, the aim of the present study was to investigate the protective effect of chrysin against MTX-induced memory impairments related to hippocampal neurogenesis. Seventy-two male Sprague Dawley rats were divided into six groups: control, MTX, chrysin (10 and 30 mg/kg), and MTX+ chrysin (10 and 30 mg/kg) groups. Chrysin (10 and 30 mg/kg) was administered by oral gavage for 15 days. MTX (75 mg/kg) was administered by intravenous injection on days 8 and 15. Spatial and recognition memories were evaluated using the novel object location (NOL) and novel object recognition (NOR) tests, respectively. Moreover, cell proliferation, neuronal cell survival, and immature neurons in the subgranular zone of the hippocampal dentate gyrus were quantified by Ki-67, bromodeoxyuridine/neuronal nuclear protein (BrdU/NeuN), and doublecortin (DCX) immunohistochemistry staining. The results of the MTX group demonstrated that spatial and recognition memories were both impaired. Furthermore, cell division reduction, neuronal cell survival reduction, and immature neuron decreases were detected in the MTX group and not observed in the co-administration groups. Therefore, these results revealed that chrysin could alleviate memory and neurogenesis impairments in MTX-treated rats.

Caffeic Acid Alleviates Memory and Hippocampal Neurogenesis Deficits in Aging Rats Induced by D-Galactose.

Hippocampal neurogenesis occurs throughout life, but it declines with age. D-galactose (D-gal) enhances cellular senescence through oxidative stress leading to neurodegeneration and memory impairment. Caffeic acid (CA) acts as an antioxidant via decreasing brain oxidative stress. This study aims to investigate the advantages of CA in alleviating the loss of memory and neurogenesis production in the hippocampus in aged rats activated by D-gal. Fifty-four male Sprague-Dawley rats were unpredictably arranged into six groups. In the D-gal group, rats were administered D-gal (50 mg/kg) by intraperitoneal (i.p.) injection. For the CA groups, rats received 20 or 40 mg/kg CA by oral gavage. In the co-treated groups, rats received D-gal (50 mg/kg) and CA (20 or 40 mg/kg) for eight weeks. The results of novel object location (NOL) and novel object recognition (NOR) tests showed memory deficits. Moreover, a decline of neurogenesis in the hippocampus was detected in rats that received D-gal by detecting rat endothelial cell antigen-1 (RECA-1)/Ki-67, 5-bromo-2'-deoxyuridine (BrdU)/neuronal nuclear protein (NeuN), doublecortin (DCX) by means of staining to evaluate blood vessel associated proliferating cells, neuronal cell survival and premature neurons, respectively. By contrast, CA attenuated these effects. Our results postulate that CA attenuated the impairment of memory in D-gal-stimulated aging by up-regulating levels of hippocampal neurogenesis.

Melatonin Attenuates Methotrexate-Induced Reduction of Antioxidant Activity Related to Decreases of Neurogenesis in Adult Rat Hippocampus and Prefrontal Cortex.

Previous studies have revealed that the side effects of anticancer drugs induce a decrease of neurogenesis. Methotrexate (MTX), one of anticancer drugs, can induce lipid peroxidation as an indicator of oxidative stress in the brain. Melatonin has been presented as an antioxidant that can prevent oxidative stress-induced neuronal damage via the activation of antioxidant enzymes associated with the increase of neurogenesis. The aims of the present study are to examine the neuroprotective effect of melatonin on the neurotoxicity of MTX on neurogenesis and the changes of protein expression and antioxidant enzyme levels in adult rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were assigned into four groups: vehicle, MTX, melatonin, and melatonin+MTX groups. The vehicle group received saline solution and 10% ethanol solution, whereas the experimental groups received MTX (75 mg/kg, i.v.) and melatonin (8 mg/kg, i.p.) treatments. After the animal examination, the brains were removed for p21 immunofluorescence staining. The hippocampus and PFC were harvested for Western blot analysis and biochemical assessments of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). The immunofluorescence result showed that coadministration with melatonin diminished p21-positive cells in the hippocampal dentate gyrus, indicating a decrease of cell cycle arrest. Melatonin reduced the levels of MDA and prevented the decline of antioxidant enzyme activities in rats receiving MTX. In the melatonin+MTX group, the protein expression results showed that melatonin treatment significantly upregulated synaptic plasticity and an immature neuron marker through enhancing brain derived neurotrophic factor (BDNF) and doublecortin (DCX), respectively. Moreover, melatonin ameliorated the antioxidant defense system by improving the nuclear factor erythroid 2-related factor 2 (Nrf2) in rats receiving MTX. These findings suggested that the effects of melatonin can ameliorate MTX toxicity by several mechanisms, including an increase of endogenous antioxidants and neurogenesis in adult rat hippocampus and PFC.

Melatonin Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats.

BACKGROUND: Valproic acid (anticonvulsant medication) has been found to inhibit histone deacetylase activity and suppress hippocampal neurogenesis, which causes memory impairment in both humans and rodents. The neurohormone melatonin, which regulates mammalian seasonal and circadian physiology, has recently been shown to have neuroprotective properties, counteracting memory impairment associated with VPA-caused hippocampal neurogenesis reduction. This study is aimed at investigating the molecular mechanisms of melatonin associated with VPA-induced hippocampal neurogenesis and memory impairment. METHODS: Male Spraque-Dawley rats received VPA (300 mg/kg) twice daily or melatonin (8 mg/kg/day) or some rats were given melatonin for 14 days during VPA administration. RESULTS: The VPA-treated rats showed a significant increase in malondialdehyde (MDA) levels in the hippocampus and p21-positive cells in the subgranular zone (SGZ) of the dentate gyrus (DG) but decreased superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. Moreover, VPA significantly decreased levels of nestin, Notchl, nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX), sex determining region Y-box 2 (SOX2), and brain-derived neurotrophic factor (BDNF). CONCLUSIONS: We found that melatonin was able to counteract these neurotoxic effects, acting as a neuroprotectant in VPA-induced memory hippocampal neurogenesis impairment by preventing intracellular oxidative stress and increasing antioxidant activity.

Hesperidin Reduces Memory Impairment Associated with Adult Rat Hippocampal Neurogenesis Triggered by Valproic Acid.

Treatment with valproic acid (VPA) deteriorates hippocampal neurogenesis, which leads to memory impairment. Hesperidin (Hsd) is a plant-based bioflavonoid that can augment learning and memory. This study aimed to understand the effect of Hsd on the impairment of hippocampal neurogenesis and memory caused by VPA. The VPA (300 mg/kg) was administered by intraperitoneal injection twice daily for 14 days, and Hsd (100 mg/kg/day) was administered by oral gavage once a day for 21 days. All rats underwent memory evaluation using the novel object location (NOL) and novel object recognition (NOR) tests. Immunofluorescent staining of Ki-67, BrdU/NeuN, and doublecortin (DCX) was applied to determine hippocampal neurogenesis in cell proliferation, neuronal survival, and population of the immature neurons, respectively. VPA-treated rats showed memory impairments in both memory tests. These impairments resulted from VPA-induced decreases in the number of Ki-67-, BrdU/NeuN-, and DCX-positive cells in the hippocampus, leading to memory loss. Nevertheless, the behavioral expression in the co-administration group was improved. After receiving co-administration with VPA and Hsd, the numbers of Ki-67-, BrdU/NeuN-, and DCX-positive cells were improved to the normal levels. These findings suggest that Hsd can reduce the VPA-induced hippocampal neurogenesis down-regulation that results in memory impairments.

Effect of metformin treatment on memory and hippocampal neurogenesis decline correlated with oxidative stress induced by methotrexate in rats.

Metformin is currently used as a first-line drug to treat patients with type 2 diabetes. Previous studies have demonstrated that metformin has antioxidant properties and reduces neuroinflammation and hippocampal neuronal cell loss, which eventually improves memory. Methotrexate (MTX) is an antimetabolite chemotherapeutic agent reported to activate cognitive impairment found in many patients. Moreover, MTX negatively affects the spatial working memory, related to neurogenesis reduction in animal models. Therefore, the present study aimed to investigate the antioxidant effect of metformin on the reduction of memory and neurogenesis caused by MTX. Male Sprague-Dawley rats were divided into four groups: control, MTX, metformin, and MTX+metformin. MTX (75 mg/kg, i.v.) was administered on days 7 and 14. Rats were administered metformin (200 mg/kg, i.p.) for 14 days. Memory was determined using novel object location (NOL) and novel object recognition (NOR) tests. Furthermore, cell cycle arrest was quantified by p21 immunostaining. Levels of neuronal protein expression, scavenging enzymes activity, and malondialdehyde (MDA) level changes in the hippocampus and prefrontal cortex were investigated. Rats receiving only MTX showed memory impairment. Decreases in scavenging enzyme activity and BDNF, DCX, and Nrf2 protein expressions levels were detected in the MTX-treated rats. In addition, MTX significantly increased p21-positive cell numbers and MDA levels. However, these adverse MTX effects were counteracted by co-administration with metformin. These results demonstrate that metformin can improve memory impairments, increase BDNF, DCX and Nrf2 protein expressions and antioxidant capacities, and decrease MDA levels in MTX-treated rats.

Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex.

Melatonin is an endogenous hormone that exhibits antioxidant functions and neuroprotective effects. The hippocampus and the prefrontal cortex (PFC) play an important role linked to working memory. 5-fluorouracil (5-FU) can induce oxidative stress and reduce neurogenesis in the subgranular zone (SGZ) of the dentate gyrus in a rat hippocampus and these alterations are related to working memory deficits. This study aimed to determine the effect of melatonin on 5-FU-induced oxidative stress that interferes with the antioxidant enzymes and protein expression levels in a rat hippocampus and PFC. A total of 68 male Sprague Dawley rats were divided into four groups: vehicle, 5-FU, melatonin and melatonin+5-FU groups. Rats were administered 5-FU (25 mg/kg, i.v.) on days 9, 12, 15, 18 and 21 and received melatonin (8 mg/kg, i.p.) at 19:00 from day 1 to day 21 of the experiment. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) levels. Antioxidant enzyme levels including glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined. p21 immunofluorescence staining and Western blotting were used to detect the cell cycle arrest and protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX) and brain derived neurotrophic factor (BDNF), respectively. The results showed that melatonin reduced the number of p21-positive cells in the SGZ of the dentate gyrus and increased Nrf2, DCX and BDNF protein expression in rats treated with 5-FU. Moreover, melatonin restored antioxidant enzyme levels and reduced oxidative stress in the hippocampus and PFC caused by 5-FU. These findings reveal a mechanism of the neuroprotective properties of melatonin against 5-FU in a rat hippocampus and PFC.

Effect of combined extracts of aged garlic, ginger, and chili peppers on cognitive performance and brain antioxidant markers in Aß-induced rats.

A combination of aged garlic, ginger, and chili peppers extracts (AGC) was studied by high-performance liquid chromatography, 2,2-diphenyl-1-picrylhydrazyl, and ferric-reducing antioxidant assays, and oxidative stress markers were analyzed in Aß1-42-induced rats. The AGC was orally administered to Wistar rats at doses of 125, 250, and 500 mg/kg body weight (AGC125, AGC250, AGC500, respectively) for 64 days. At day 56, Aß1-42 was injected via both sides of the lateral ventricles. The effects of the AGC on spatial and recognition memory were examined using a Morris water maze and novel object recognition tasks. Rats induced with Aß1-42 exhibited obvious cognitive deficits, as demonstrated by their increased escape latency time (ET) and decreased retention time (RT) and percentage of discriminative index (DI). When compared with the control group, all AGC-treated rats showed significantly shorter ETs and higher DIs during the 5-min delay testing phase. Rats treated with AGC250 also had significantly longer RTs. Administration of Aß1-42 significantly increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in the rat brain homogenate. Pretreatment with the AGC caused significant increases in SOD, GPx, and CAT activities, as well as a significant decrease in MDA in the rat brain homogenates after Aß-induced neurotoxicity. Our results suggested that an AGC may ameliorate cognitive dysfunction in Aß-treated rats due to its role in the upregulation of SOD, GPx, and CAT.

Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat.

Methotrexate (MTX) induces the formation of reactive oxygen species (ROS) and leads to neurotoxicity. The drug also negatively impacts neurogenesis and memory. Hesperidin (Hsd) is a major flavanoid with multiple beneficial pharmacological effects such as anti-oxidation, anti-inflammation, and neuroprotective effects. The aim of our study was to investigate the neuroprotective effects of Hsd against MTX-induced alterations in oxidative stress and neurogenesis. Sprague Dawley rats were divided into four groups: 1) a vehicle group, which received saline and propylene glycol, 2) an Hsd group, which was orally administered with Hsd (100 mg/kg) for 21 days, 3) an MTX group, which received MTX (75 mg/kg) by intravenous injection on days 8 and 15, and 4) an MTX + Hsd group, which received both MTX and Hsd. After treatment with MTX, p21-positive cells had increased significantly and doublecortin (DCX) expression in the hippocampus had decreased significantly. Treatment with MTX also increased malondialdehyde (MDA) in both the hippocampus and prefrontal cortex and decreased levels of brain-derived neurotropic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and prefrontal cortex. Additionally, there were significant decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus and prefrontal cortex in the MTX group. However, co-treatment with Hsd ameliorated the negative effects of MTX on neurogenesis, oxidative stress, and antioxidant enzymes. These findings suggest that Hsd may be able to prevent neurotoxic effects of MTX by reducing oxidative stress and enhancing hippocampal neurogenesis.

Metformin alleviates memory and hippocampal neurogenesis decline induced by methotrexate chemotherapy in a rat model.

Methotrexate (MTX) is a chemotherapeutic drug commonly used to treat cancers that has an adverse effect on patients' cognition. Metformin is a primary treatment for type 2 diabetes mellitus that can pass through the blood-brain barrier. Metformin has neuroprotective actions, which can improve memory. In the present study, we examined the ability of metformin in MTX chemotherapy-generated cognitive and hippocampal neurogenesis alterations. Male Sprague-Dawley rats were allocated into control, MTX, metformin, preventive, and throughout groups. MTX (75 mg/kg/day) was given intravenously on days 7 and 14 of the study. Metformin (200 mg/kg/day) was injected intraperitoneally for 14 days. Some of the MTX-treated rats received co-treatment with metformin once a day for either 14 (preventive) or 28 days (throughout). After treatment, memory ability was evaluated using novel object location and novel object recognition tests. Ki67 (proliferating cells), BrdU (survival cells), and doublecortin (immature neurons, DCX) positive cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus were quantified. We found that reductions of cognition, the number of proliferating and survival cells and immature neurons in the SGZ were ameliorated in the co-treatment groups, which suggests that metformin can prevent memory and hippocampal neurogenesis impairments induced by MTX in adult rats.

Chrysin Protects against Memory and Hippocampal Neurogenesis Depletion in D-Galactose-Induced Aging in Rats.

The interruption of hippocampal neurogenesis due to aging impairs memory. The accumulation of D-galactose (D-gal), a monosaccharide, induces brain aging by causing oxidative stress and inflammation, resulting in neuronal cell damage and memory loss. Chrysin, an extracted flavonoid, has neuroprotective effects on memory. The present study aimed to investigate the effect of chrysin on memory and hippocampal neurogenesis in brains aged using D-gal. Male Sprague-Dawley rats received either D-gal (50 mg/kg) by i.p. injection, chrysin (10 or 30 mg/kg) by oral gavage, or D-gal (50 mg/kg) and chrysin (10 or 30 mg/kg) for 8 weeks. Memory was evaluated using novel object location (NOL) and novel object recognition (NOR) tests. Hippocampal neurogenesis was evaluated using Ki-67, 5-bromo-2'-deoxyuridine (BrdU), and doublecortin (DCX) immunofluorescence staining to determine cell proliferation, cell survival, and number of immature neurons, respectively. We found that D-gal administration resulted in memory impairment as measured by NOL and NOR tests and in depletions in cell proliferation, cell survival, and immature neurons. However, co-treatment with chrysin (10 or 30 mg/kg) attenuated these impairments. These results suggest that chrysin could potentially minimize memory and hippocampal neurogenesis depletions brought on by aging.

Melatonin attenuates 5-fluorouracil-induced spatial memory and hippocampal neurogenesis impairment in adult rats.

AIMS: Treatment with 5-fluorouracil (5-FU) can cause impairment to adult hippocampal neurogenesis, resulting in cognitive deficits. As melatonin has been shown to enhance memory and hippocampal neurogenesis in animal models, this research investigated the neuroprotective effects of melatonin against spatial memory and hippocampal neurogenesis impairment in 5-fluorouracil (5-FU)-treated rats. MATERIALS AND METHODS: Four-Five weeks old male Spraque-Dawley rats weighing between 180 and 200 g were used. Animals were maintained under standard laboratory conditions with 25 °C and 12 h light/dark cycle. Animal were administered intravenous (i.v.) injections of 5-FU (25 mg/kg) 5 times every 3 days starting on day 9 of the experiment. The rats were divided into preventive, recovery, and throughout groups and co-treated with melatonin (8 mg/kg, i.p.) once daily (at 7.00 pm) for 21 days prior to, after, and throughout 5-FU treatment, respectively. Spatial memory was assessed using a novel object location (NOL) test. Hippocampal neurogenesis was then examined using Ki67, bromodeoxyuridine (BrdU), and doublecortin (DCX) immunohistochemistry staining. KEY FINDINGS: Melatonin administration was able to both protect the subjects from and reverse spatial memory deficits. 5-FU was also found to reduce the generation of hippocampal newborn neurons. However, co-treatment with melatonin ameliorated the reductions in neurogenesis caused by 5-FU. SIGNIFICANCE: These findings suggest that melatonin administration was able to ameliorate the 5-FU-induced spatial memory deficits associated with neurogenesis. The present work will be valuable for patients who suffer memory deficits from 5-FU chemotherapy.