Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.

BACKGROUND: Diffuse midline gliomas (DMG) pose a grave threat as a malignant tumor primarily affecting children in the pons region. These tumors exhibit a distinct and heightened resistance to therapeutic interventions, coupled with exceptionally aggressive behavior. METHODS: In this study, we accessed DMG data from the Gene Expression Omnibus (GEO) database. Subsequently, we performed functional annotation and conducted pathway enrichment analysis as well as gene set enrichment analysis (GSEA). Constructing a protein-protein interaction (PPI) network, we identified pivotal hub genes. To evaluate the impact of these hub genes on immune infiltration, we employed the CIBERSORT algorithm. Furthermore, to bolster our findings, we conducted a single-cell analysis. RESULTS: Our findings indicate the involvement of CD8A, IL7R, and ICAM1 in immune responses targeting diverse immune cell types, such as T cells, neutrophils, NK cells, dendritic cells, γδ T cells, and Macrophages M1. Additionally, the presence of immune checkpoints, including IDO1 and TIGIT, likely contributes to intratumoral immunosuppression, thereby fostering the development of an aggressive phenotype and resistance in pediatric DMG. CONCLUSION: In conclusion, the collective findings of our study suggest the potential role of CD8A, IL7R, and ICAM1 as innovative biomarkers for diagnosing and prognosticating pediatric DMG. Moreover, these molecules hold promise as therapeutic targets in the management of this disease. The implications of our research underscore the importance of exploring these novel avenues for improved patient outcomes.

Broadband single-molecule fluorescence enhancement based on self-assembled Ag@Au dimer plasmonic nanoantennas.

Dimer optical antennas (OAs) enable great fluorescence enhancement and excitation volume reduction and hence potentially can be a very useful tool for single-molecule detection. The realization of broadband fluorescence enhancement with a dimer OA remains an essential step for its usage in multi-color single-molecule fluorescence (SMF) detection. Although silver dimer OAs have been shown to be able to yield broadband fluorescence enhancement over the visible spectrum, they are amenable to oxidization, hard to functionalize, and could cause cytotoxicity. To overcome these limitations, in this work, we took advantage of nano-sized silver due to its optical properties and gold due to its chemical properties and developed an ameliorated Ag@Au dimer OA in terms of its overall performance. The Ag@Au nanoparticle in the dimer OA contains a 70 nm silver core and an ultra-thin (∼1-5 nm) gold shell which play a key role in its optical responses. Furthermore, we employed three typical dyes, i.e., FAM, TAMRA and Cy5, representing the blue, yellow and red ranges, respectively, and characterized their single-molecule fluorescence enhancements in the presence of Au or Ag@Au OAs. Our results indicate that, in contrast to its Au counterpart, the Ag@Au dimer OA prepared here can greatly improve its optical response in the blue range and eventually achieve broadband fluorescence enhancement throughout almost the whole visible spectral range. Meanwhile, it also maintains good chemical stability and accessibility to functionalization. Such Ag@Au dimer OAs are thus expected to have many important applications in the future, including single-molecule sequencing and multi-color biosensing.

Sex-Related Differences in the Incidence and Development of Carotid Plaques in a Low-Income Chinese Population-A Prospective Cohort Study.

Purpose: More than 150 million people are estimated to have been examined for the presence of carotid plaques (CPs) in China; a sex-related imbalance in the prevalence exists. However, the relationship between sex and the incidence of CP development is unclear, especially in low-income areas of China. Hence, this study aimed to identify the sex differences in CP development and CP burden in both sexes in this population. Methods: The study population included individuals aged ≥45 years in a rural area of Tianjin, China. Carotid ultrasonography was performed in the 2014 and 2019 cohorts, and information on carotid ultrasonography, including the formation and number of CPs, was collected twice. Logistic analyses were used to investigate the predictors of CP formation and numbers of plaques. Results: A total of 1479 participants were analyzed. The incidence of CP was 20.3% and 29.0% in women and men, respectively. In women, high low-density lipoprotein cholesterol (LDL-C) levels was independent predictors of CP formation (RR: 1.217, 95%CI: 1.010, 1.461; P=0.039). For men, the corresponding predictors were hypertension, alcohol consumption, and low high-density lipoprotein cholesterol (HDL-C) levels (all P<0.05); none of the examined factors were associated with plaque numbers. Conclusion: In the study population, men had a higher incidence of plaque than women. Predictors of CP are different in men and women. LDL-C control is critical for moderating atherosclerosis in women; in men, managing blood pressure, stopping alcohol consumption, and controlling HDL-C levels are important.

Distribution and assessment of heavy metals in suspended particles in the Sundarban mangrove river, Bangladesh.

The suspended particulate matter (SPM) is an important carrier of heavy metals transportation from land to sea, so it is significant to study the heavy metal pollution in SPM. The distribution and assessment of five heavy metals (Mn, Cr, Ni, Cu, and Pb) in SPM collected from Passur River and its estuary in Sundarban were studied in combination with water temperature, salinity, and turbidity. The results show that the heavy metal content and distribution in SPM are mainly controlled by runoff input, hydrodynamic process and the interaction process of salt and fresh water in estuaries. The quality evaluation results of heavy metals in SPM show that pollution degree is light. Studies on the heavy metals in SPM are of great significance to comprehensively evaluate regional pollution status and carry out early warning.

Typhoon Fung-wong (2008) induced heavy metals secondary pollution in Quanzhou Bay, southeast of China.

The concentrations of Cr, Ni, Cu, Zn, As, Cd, Pb, and Al in suspended particles were measured, and temperature, salinity, flow velocity and direction during a tidal cycle were observed before and after Typhoon Fung-wong at six stations in Quanzhou Bay, respectively. The comparison results show that, after the typhoon, the salinity in Quanzhou Bay decreased, whereas the concentrations of heavy metals increased by a factor of between 2 and 10, and the high heavy metal concentration corresponded to the low value of ratio between heavy metals and Al (HMs/Al), suggesting that these increased heavy metals were mainly from natural sources. Instantaneous unit width flux calculations for heavy metals at different stations indicate that sediments are an important source of heavy metals in suspended particles under the influence of typhoon, which has significantly contribution to understanding the impact of typhoons on the heavy metal pollution in the coastal area.

H19/miR-675-5p Targeting SFN Enhances the Invasion and Metastasis of Nasalpharyngeal Cancer Cells.

AIMS: The aim is to study the role of miR-675-5p coded by long non-coding RNA H19 in the development of Nasopharyngeal Cancer (NPC) and whether miR-675-5p regulates the invasion and metastasis of NPC through targeting SFN (14-3-3σ). The study further validated the relationship between H19, miR-675-5p and SFN in NPC and their relationship with the invasion and metastasis of NPC. METHODS: Western blot was used to detect the expression of 14-3-3σ protein in immortalized normal nasopharyngeal epithelial cells NP69 and different metastatic potential NPC cells, 6-10B and 5-8F. At the same time, to find out the relationship between 14-3-3σ protein and the expression of H19 and miR-675-5p, the expression of H19 and miR-675-5p in normal nasopharynx epithelial cells NP69 and varied nasopharyngeal carcinoma cells 6-10B and 5-8F were quantified by real-time PCR. MiR-675-5p mimic and inhibitor were transfected into NPC 6-10B to over-express and down-express miR-675-5p; miR-675-5p mimic negative control and inhibitor negative control were transfected into NPC 6-10B as control groups. The effect of over-expression and down-expression by miR-675-5p on the expression of 14-3-3σ protein was detected by Western blotting. The 3'-UTR segments of SFN, containing miR-675-5p binding sites were amplified by PCR and the luciferase activity in the transfected cells was assayed to detect whether SFN is the direct target of miR-675-5p. Transwell and scratch assays were used to verify the changes in NPC invasion and metastasis ability of mimics and inhibitors transfected with miR-675-5p. RESULTS: The expression of 14-3-3σ protein in normal nasopharynx epithelial cells NP69 is significantly higher than in varied nasopharyngeal carcinoma cells, 6-10B and 5-8F (P<0.05), and the 14-3-3σ protein levels in low-metastatic nasopharyngeal carcinoma cell 6-10B is higher than in high-metastatic nasopharyngeal carcinoma cell 5-8F. The expression of H19 and miR-675-5p are significantly higher in NPC cells than in NP69 cell (P<0.05). The expression of H19 and miR-675-5p in high-Metastatic nasopharyngeal carcinoma cell 5-8F was higher than in low-Metastatic nasopharyngeal carcinoma cell 6-10B. The expression of 14-3-3σ protein in miR-675-5p mimic cells was significantly lower than in mimic NC (negative control) group and blank control group. However, compared with the blank control group, mimic NC showed no significant difference in 14-3-3σ protein between the two groups. The miR-675-5p inhibitor group was significantly higher than the inhibitor NC group and the blank control group (p<0.05), but there was no significant difference in the expression of 14-3-3σ protein in the inhibitor NC group and the blank control group (p>0.05). Dual-luciferase reporter assay system shows the 3'-UTR segments of SFN containing miR-675-5p binding sites. SFN was the target gene of miR-675-5p. CONCLUSION: 14-3-3σ is downregulated in NPC and is involved in the development of NPC. H19 and miR- 675-5p are upregulated in NPC, which is related to the development of NPC. The over-expression of miR- 675-5p inhibits the expression of 14-3-3σ protein. SFN is the target gene of miR-675-5p. MiR-675-5p targets SFN, downregulates its protein expression and promotes the invasion and metastasis of NPC.

Evolution of sedimentary organic matter in a small river estuary after the typhoon process: A case study of Quanzhou Bay.

Extreme weather events occur frequently under global warming scenarios and have an important impact on the global carbon cycle. Compared to large rivers, small rivers are more sensitive to extreme weather events (such as typhoons). This paper reports the results of a study carried out in the Quanzhou Bay to explore the evolution of small river estuarine sedimentary organic matter after typhoon process using measurements of the grain-size, total organic carbon (TOC), total nitrogen (TN) and δ13C of surface sediment samples collected 2-3 days and a month, respectively, after typhoon Matmo landing in 2014. The results show that the contents of TOC and TN in the sediments, which gradually decrease from the estuary to the outer sea of Quanzhou Bay, decreased approximately 13% and 16%, respectively, a month later compared with 2-3 days after typhoon landing. The significant decrease occurred in the Jinjiang River estuary and along the South Channel of Quanzhou Bay, while the North Channel and Luoyangjiang River estuary retained high levels of TOC and TN. The results of δ13C values and TOC/TN ratios show that the organic matter in the sediment of the Quanzhou Bay was a mixture derived from C3 terrestrial plants and marine algae. The terrestrial organic matter was mainly deposited in the Jinjiang River estuary 2-3 days after typhoon landing and then spread along the tidal channel to the outer sea a month later. It indicates that the hydrodynamic forces stirred sedimentary organic matters that were input and settled during typhoon, and transported later along the North and South Channel to the outer sea. Some of those organic matters were accumulated in the North Channel during the transport process. The results provide significant meaning for the carbon cycle and material flux study on the coastal and margin seas.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells.

BACKGROUND: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. METHODS: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. RESULTS: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. CONCLUSION: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1.

Luteolin is a flavonoid compound derived from Lonicera japonica Thunb, which has been reported to exert anticancer effects on different types of tumors. miRNAs are a kind of endogenous non-coding small RNAs, which involved in occurrence and development of multi cancer, including miR-34a. However, the relationship between miR-34a and luteolin's susceptibility to cancer cells still remains unclear. In this study, we explored the roles of miR-34a and the effects of luteolin on GC cells as well as the underlying mechanism of miR-34a in mediating the susceptibility of GC cell to luteolin. Retrospectively study revealed that miR-34a expression was downregulated in human primary GC tissues compared with non-tumor tissues and low miR-34a expression was associated with a significantly shorter overall survival and disease-free survival. MiR-34a overexpression could inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPK /ERK pathways. Luteolin decreased viability of GC cells in a dose-dependent manner. Meanwhile, miR-34a was found to be markedly upregulated in GC cells induced by luteolin and decreased miR-34a level was found in the artificial luteolin-resistant GC cells. Upregulation of miR-34a in luteolin-resistant GC cell could enhance the sensibility of GC cells to luteolin. On the other hand, miR-34a inhibitor could partly counter the anticancer effect of luteolin. In a further assay, we also found that targeting miR-34a could mediate the susceptibility of mouse xenografts to luteolin. Subsequent study found that HK1 was a direct target of miR-34a and downregulated HK1 mRNA or protein levels were presented after miRNA-34a overexpression in GC cells. Moreover, HK1 protein levels was decreased after luteolin treatment and partly restored when co-treated with luteolin and miR-34a inhibitor. Downregulation of HK1 in luteolin-resistant GC cell could increase the cell's sensitivity to luteolin. Therefore, our findings firstly suggested that miR-34a could modulate the susceptibility of gastric cancer cell to luteolin via targeting HK1, potentially benefiting GC patients' treatment in the future.

Distribution of heavy metals in seafloor sediments on the East China Sea inner shelf: Seasonal variations and typhoon impact.

Based on concentrations and distributions of heavy metals, grain size and loss on ignition (LOI) in the seafloor sediments acquired during three surveys in winter and in summer (before and after typhoon Morakot) in the mud deposition center off the Fujian-Zhejiang coast, East China Sea, the seasonal and typhoon-induced variations of heavy metals in seafloor sediments are discussed. It is found that different concentrations of heavy metals occurred in seafloor sediments, but their distribution patterns were similar, gradually decreasing from near-shore to offshore. The distribution of heavy metals was correlated with grain size and LOI in seafloor sediments, which showed significant seasonal variations and typhoon's impact. Based on these results, a conceptual evolution model was built about the seasonal and typhoon's impact on the deposition environment of heavy metals, which has implications for understanding the migration, settling, and burial processes of heavy metals in the sea.

Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury.

PURPOSE: Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown that infusion of human umbilical cord blood-derived endothelial colony-forming cells improves outcomes in mice subjected to experimental traumatic brain injury (TBI). However, the efficiency of cell transplantation is not satisfactory. Oxidative stress plays a significant role in the survival of transplanted cells following ischemic reperfusion injury. This observational clinical study investigated the correlation between the number of circulating EPCs and plasma levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA). MATERIALS AND METHODS: Peripheral blood samples were collected from 20 patients with mild TBI at day-1, day-2, day-3, day-4, and day-7 post TBI. The number of circulating EPCs and the plasma levels of SOD and MDA were measured. RESULTS: The average of circulating EPCs in TBI patients decreased initially, but increased thereafter, compared with healthy controls. Plasma levels of SOD in TBI patients were significantly lower than those in healthy controls at day-4 post-TBI. MDA levels showed no difference between the two groups. Furthermore, when assessed on day-7 post-TBI, the circulating EPC number were correlated with the plasma levels of SOD and MDA. CONCLUSION: These results suggest that the number of circulating EPCs is weakly to moderately correlated with plasma levels of SOD and MDA at day-7 post-TBI, which may offer a novel antioxidant strategy for EPCs transplantation after TBI.

Relationship of Circulating CXCR4+ EPC with Prognosis of Mild Traumatic Brain Injury Patients.

To investigate the changes of circulating endothelial progenitor cells (EPCs) and stromal cell-derived factor-1α (SDF-1α)/CXCR4 expression in patients with mild traumatic brain injury (TBI) and the correlation between EPC level and the prognosis of mild TBI. 72 TBI patients (57 mild TBI, 15 moderate TBI patients) and 25 healthy subjects (control) were included. The number of circulating EPCs, CD34+, and CD133+ cells and the percentage of CXCR4+ cells in each cell population at 1,4,7,14,21 days after TBI were counted by flow cytometer. SDF-1α levels in serum were detected by ELISA assay. The patients were divided into poor and good prognosis groups based on Extended Glasgow Outcome Scale and Activity of Daily Living Scale at 3 months after TBI. Correlation analysis between each detected index and prognosis of mild TBI was performed. Moderate TBI patients have higher levels of SDF-1α and CXCR4 expression than mild TBI patients (P < 0.05). The percentage of CXCR4+ EPCs at day 7 post-TBI was significantly higher in mild TBI patients with poor prognosis than the ones with good prognosis (P < 0.05). HAMA and HAMD scores in mild TBI patients were significantly lower than moderate TBI patients (P < 0.05) in early term. The percentage of CXCR4+ EPCs at day 7 after TBI was significantly correlated with the prognosis outcome at 3 months. The mobilization of circulating EPCs can be induced in mild TBI. The expression of CXCR4+ in EPCs at 7 days after TBI reflects the short-term prognosis of brain injury, and could be a potential biological marker for prognosis prediction of mild TBI.

Clinical Significance of miR-149 in the Survival of Patients with Laryngeal Squamous Cell Carcinoma.

MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study. In vitro studies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P < 0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test, P < 0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression. In vitro studies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression.

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces.

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm (101.32 ± 11.16 kPa), 2.6 ± 0.16 atm (263.44 ± 16.21 kPa), and 3.6 ± 0.16 atm (364.77 ± 16.21 kPa), respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

Role of regulatory T cell in clinical outcome of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a life-threatening disease worldwide. Regulatory T cells (Treg cells) were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4 + cells that express CD25 and transcription factor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI. METHODS: A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University (Tianjin, China). Forty patients and 30 healthy controls were recruited from August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1, 4, 7, 14, and 21 days after TBI. Blood sample (1 ml) was withdrawn in the morning and processed within 2 h. RESULTS: There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1 st day after TBI. Treg level was decreased on the 4 th day, climbed up on the 7 th day and peaked on 14 th day after TBI. Treg cells declined to the normal level on 21 th day after TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4 + mononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 + mononuclear cells in the first 14 days. CONCLUSIONS: The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.

Impairment of synaptic plasticity in hippocampus is exacerbated by methylprednisolone in a rat model of traumatic brain injury.

Patients with traumatic brain injury (TBI) exhibit impaired cognitive capability that is exacerbated with methylprednisolone (MP). Since long-term potentiation (LTP) is a leading cellular model underlying learning, we hypothesize that MP disturbs the electrophysiological character in the hippocampus by decreasing the number of interneurons post-traumatically in the dentate gyrus (DG) and cornu ammonis3 (CA3) regions, resulting in learning deficits. To test this hypothesis, we investigated the alterations of learning abilities and correlated the alternation with hippocampal synaptic plasticity in rats receiving lateral fluid percussion injury (FPI) and being treated with MP. We found that MP aggravates the spatial learning deficiency and changes in the excitability of the DG and cornu ammonis1 (CA1) areas in rats subjected to FPI. The functional and electrophysiological deficits are associated with a decrease in the number of parvalbumin-immunoreactive (PV-IR) and cholecystokinin-immunoreactive (CCK-IR) GABAergic cells. The data suggest that MP therapy may decrease the number of DG interneurons in post-traumatic hippocampus, resulting in the aggravated deficits of learning ability induced by TBI.

Dexamethasone exacerbates spatial acquisition deficits after traumatic brain injury in rats.

OBJECTIVES: Given after traumatic brain injury (TBI), Dexamethasone (DXM) reduces cerebral edema but impairs retrograde memory. This study was designed to test the hypothesis that administration of DXM to rats with TBI promotes learning deficits that are correlated with the morphological changes of hippocampal pyramidal neurons. METHODS: Adult male Wistar rats were subjected to fluid percussion injury (FPI), received DXM (5 and 10 mg/kg), and then trained for spatial acquisition. Brain sections were examined by H.E. and Golgi impregnation to quantitatively measure the morphological changes of hippocampal pyramidal neurons. RESULTS: The latency and path length were significantly higher in rats with FPI than those in control groups, particularly in rats receiving post-trauma high-dose DXM. At the same time, Golgi impregnation revealed a significant decrease in the number of apical and basal dendrites of pyramidal neurons of ipsilateral hippocampus in rats after injury, but the decrease was greatest of CA3 pyramidal neurons of ipsilateral hippocampus in injured rats that also received high-dose DXM. DISCUSSION: These findings indicate that the administration of high-dose DXM after TBI could worsen the dendritic atrophy of hippocampal CA3 pyramidal neurons and, as a result, exacerbate spatial acquisition deficits.