Activation of peroxisome proliferator-activated receptor ß/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-ß/δ is a transcription factor that belongs to the nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-ß/δ (GW0742) in animal models of acute ischemic stroke. Using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo, we have investigated the effect of pretreatment with GW0742 before MCAO. METHODS: The neuroprotective effect of GW0742 against acute ischemic stroke was evaluated by the neurologic deficit score (NDS), dry-wet weight, and 2,3,5-triphenyltetrazolium chloride staining. The levels of interleukin (IL)-1ß, nuclear factor (NF)-κB, and tumor necrosis factor (TNF)-α were detected by an enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were detected by Western blot. The apoptotic cells were counted by in situ terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS: The pretreatment with GW0742 significantly increased the expression of Bcl-2, and significantly decreased in the volume of infarction, NDS, edema, expressions of IL-1ß, NF-κB, TNFα, and Bax, contents of iNOS and the apoptotic cells in infarct cerebral hemisphere compared with rats in the vehicle group at 24 hours after MCAO. CONCLUSIONS: The study suggests the neuroprotective effect of the PPAR-ß/δ ligand GW0742 in acute ischemic stroke by a mechanism that may involve its anti-inflammatory and antiapoptotic action.

Protective effect of Homer 1a on tumor necrosis factor-α with cycloheximide-induced apoptosis is mediated by mitogen-activated protein kinase pathways.

Although Homer 1, of the postsynaptic density, regulates apoptosis, the signaling mechanisms are not fully elucidated. In this study, we found that tumor necrosis factor-α (TNF-α)/cycloheximide (CHX) treatment transiently increased Homer 1a (the short variant of Homer 1), but did not affect Homer 1b/c (the long variant of Homer 1). Overexpression of Homer 1a blocked TNF-α/CHX-induced apoptotic cell death, whereas inhibition of Homer 1a induction enhanced the pro-apoptotic effect of TNF-α/CHX treatment. Moreover, brain-derived neurotrophic factor, as a potential activator of endogenous Homer 1a, inhibited apoptotic cell death after TNF-α/CHX treatment through induction of Homer 1a. Since three major mitogen-activated protein kinase (MAPK) pathways have important roles in apoptosis, we examined if Homer 1a is involved in the effects of MAPK pathways on apoptosis. It was shown that inhibition of the ERK1/2 pathway increased the expression and the protective effect of Homer 1a, but inhibition of the p38 pathway produced the opposite effect. Cross-talk among MAPK pathways was also associated with the regulation of Homer 1a during apoptotic cell death. Blocking the p38 pathway increased the activity in the ERK1/2 pathway, while inhibition of ERK1/2 pathway abolished the effect of p38 inhibitor on Homer 1a. Furthermore, Homer 1a reversely affected the activation of MAPK pathways. These findings suggest that Homer 1a plays an important role in the prevention of apoptotic cell death and contributes to distinct regulatory effects of MAPK pathways on apoptotic cell death.

Primary frontoparietal lobe convexity germinoma with dural invasion mimics meningioma.

Intracranial germinomas are rare and account for only 0.4-3.4% of primary intracranial tumors. They develop mainly in the midline structures in adolescents. The pineal gland is the most common site of this tumor. Here, we describe an unusual case of a giant primary intracranial germinoma located in the intracranial hemisphere with radiological findings that mimicked a meningioma. The clinical diagnosis of the intracranial germinoma was difficult because of its unusual clinical presentation, the location of the lesion, and atypical imaging findings. Based on this case study, we suggest that germinoma might be a possible diagnosis when a tumor of the hemispheres with dura invasion mimics meningioma, especially in young patients. Furthermore, we recommend that frozen biopsy sections should be taken routinely during surgery to aid in rapid diagnosis and effective therapy.

The role of excitatory amino acid transporters in cerebral ischemia.

Glutamate is an excitatory neurotransmitter that plays a major role in the pathogenesis of ischemia brain injury. The regulation of glutamate neurotransmission is carried out by excitatory amino acid transporters (EAATs) that act through reuptake of glutamate into cells. EAATs may also release glutamate into the extracellular space in a calcium-independent manner during ischemia and dysfunction of EAATs is specifically implicated in the pathology of cerebral ischemia. Recent studies show that up-regulation of EAAT2 provides neuroprotection during ischemic insult. This review summarizes current knowledge regarding the role of EAATs in cerebral ischemia.

Up-regulation of heme oxygenase-1 attenuates brain damage after cerebral ischemia via simultaneous inhibition of superoxide production and preservation of NO bioavailability.

Cerebral ischemia exacerbates neuronal death and neurological dysfunction. Evidence supports the involvement of oxidative/nitrative stress in the pathophysiology of cerebral ischemia. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism, possessing potent anti-oxidant and anti-apoptosis effects. In transgenic mice, HO-1 overproduction is neuroprotective against cerebral ischemia injury, but by unclear mechanisms. The present study determined whether treatment with adenoviral vector overexpressing HO-1 (Ad-HO-1) attenuates post-ischemic brain damage via reduction of oxidative/nitrative stress. After focal cerebral ischemia, Ad-HO-1 reduced lipid peroxidation and protein nitration, decreased infarct volume, and attenuated neurologic deficits. Zinc protoporphyrin IX (ZnPP IX, a specific HO-1 inhibitor) blocked Ad-HO-1 mediated effects against ischemic brain damage. Although Ad-HO-1 slightly reduced ischemic brain NO concentrations, Ad-HO-1 treatment significantly inhibited cerebral expression of iNOS protein expression, without significant effect upon nNOS or eNOS expression compared to vehicle after focal cerebral ischemia. Ad-HO-1 preserved NO bioavailability by increasing eNOS phosphorylation during ischemia compared to vehicle. Together, our results suggest that Ad-HO-1 attenuates post-ischemic brain damage via simultaneous reduction of oxidative/nitrative stress and preservation of NO bioavailability.

VEGF protects rat cortical neurons from mechanical trauma injury induced apoptosis via the MEK/ERK pathway.

Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological dysfunction or death. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and vascular permeability. Recently, VEGF has been identified as a neurotrophic factor and has been implicated in the pathogenic mechanisms of TBI. However, the possible mechanisms of VEGF in primary or secondary injuries after TBI are largely unknown. The present study attempted to determine whether VEGF has a protective effect on primary cortical neurons against mechanical trauma injury, which is an in vitro insult mimicking traumatic brain injury. We found that pretreatment of primary cortical neurons in culture with VEGF decreased neuronal death in a concentration-dependent manner, and VEGF counteracted the mechanical trauma mediated apoptotic death of cultured cortical neurons. VEGF up-regulates the activity of ERK (extracellular signal-regulated kinase) in cultured cortical neurons and U0126 (a mitogen activated protein kinase kinase (MEK) inhibitor) suppressed VEGF induced activity of ERK. Furthermore, incubation of cells with U0126 attenuated the ability of VEGF to protect neurons against mechanical trauma-induced apoptosis. Therefore, the present study supports the notion that MEK/ERK pathway is involved in VEGF mediated neuroprotection against mechanical trauma injury.

Salvianolic acid B attenuates brain damage and inflammation after traumatic brain injury in mice.

Salvianolic acid B (SalB), a bioactive compound isolated from the Chinese medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in in vitro and in vivo studies. Here, we investigated the protective effects of SalB on traumatic brain injury (TBI) in mice. When administered within 2 h after TBI onset, SalB (25 mg/kg) reduced brain edema, lesion volume and motor functional deficits, and improved spatial learning and memory abilities. Moreover, SalB treatment inhibited the neutrophil infiltration and microglial activation at 48 h after TBI. Enzyme-linked immunosorbent assay (ELISA) for brain tissue homogenates was performed at 24 h after TBI to evaluate the expression of inflammation-related cytokines. The results showed that SalB suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1ß, whereas enhanced the expression of anti-inflammatory cytokines IL-10 and TGF-ß1. All of these findings extended the protective role of SalB in the model of TBI and suggested that these protective effects might be associated with its anti-inflammatory activities. Thus SalB may have therapeutic potential for patients with TBI and perhaps other forms of acute brain injury.

Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress.

Traumatic brain injury (TBI) is a leading cause of mortality and disability among the young population. It has been shown that hydrogen gas (H(2)) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical (OH, the most cytotoxic ROS). Recently, we have found that H(2) inhalation significantly improved the survival rate and organ damage of septic mice. In the present study, we investigated the effectiveness of H(2) therapy on brain edema, blood-brain barrier (BBB) breakdown, neurological dysfunction and injury volume in TBI-challenged rats. In addition, we investigated the effects of H(2) treatment on the changes of oxidative products and antioxidant enzymes in brain tissue of TBI-challenged rats. Hydrogen treatment was given by exposure to 2% H(2) from 5 min to 5h after sham or TBI operation, respectively. Here, we found that TBI-challenged rats showed significant brain injuries characterized by the increase of BBB permeability, brain edema and lesion volume as well as neurological dysfunction, which was significantly attenuated by 2% H(2) treatment. In addition, we found that the decrease of oxidative products and the increase of endogenous antioxidant enzymatic activities in the brain tissue may be associated with the protective effects of H(2) treatment in TBI-challenged rats. The present study supports that H(2) inhalation may be a more effective therapeutic strategy for patients with TBI.

Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats.

Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1ß and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1ß and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke.

[Study on factors related to top 10 junk food consumption at 8 to 16 years of age, in Haidian District of Beijing].

OBJECTIVE: To study the current situation of ten types of junk food consumption (assessed by World Health Organization) among children and adolescent as well as the contributing factors in Haidian District, Beijing so as to provide evidence for developing preventive and control measures and interventions. METHODS: A questionnaire survey was conducted to investigate the consumption of ten types of junk food practices in 1019 children and adolescent aged 8-16 years in Beijing Haidian District. RESULTS: One month prior to the study, 97.50% of the children and adolescent had eaten at least one type of junk food and 15.88% of them had eaten all types of them. Rates on having eaten deep fried food, pickled food, processed meat products, biscuits, coke or alike drinks, convenience/fast food, canned food, dried or preserved fruit, cold and sweet food, barbecue food etc. appeared to be 70.43%, 60.14%, 79.72%, 64.24%, 69.63%, 78.72%, 42.16%, 51.95%, 68.13%, 60.14% respectively. The rate on eaten more than once a day of these ten types were 26.95%, 36.88%, 34.84%, 32.97%, 27.40%, 28.18%, 37.91%, 26.15%, 37.39%, 22.10% respectively. The rates for "do not like" and "dislike" these ten types junk food were 10.96%, 27.42%, 7.08%, 12.11%, 6.56%, 6.59%, 17.80%, 13.59%, 3.42%, 5.19% respectively. Most of the children and adolescent ate junk food mainly during breakfast at home. Most of the surveyed children and adolescent did not have correct idea on nutrition of junk food. They received the information of junk food mainly from sources as advertisement on TV (67.95%), mother (9.02%), newspaper or magazines (6.71%). Many factors, such as individual factors (including physiological and psychological situations), social factors, family factors and the characteristics of food contributed to the eating junk food practices of children and adolescent. CONCLUSION: Eating junk food is a popular event among children and adolescent in Beijing Haidian District. Education strategies on nutrition should be developed and launched in order to help children develop their own healthy eating behaviors.