OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects

Brain Ischemia ; pathology ; physiopathology ; Humans ; Neoplasm Proteins ; metabolism ; Pyroptosis ; physiology ; Signal Transduction ; physiology

A 68-year-old man presented with a three-week history of rapidly progressive dementia, gait ataxia and myoclonus. Subsequent electroencephalography showed periodic sharp wave complexes, and cerebrospinal fluid assay revealed the presence of a 14-3-3 protein. A probable diagnosis of sporadic Creutzfeldt-Jakob disease was made, which was further supported by magnetic resonance (MR) imaging of the brain showing asymmetric signal abnormality in the cerebral cortices and basal ganglia. The aetiology, clinical features, diagnostic criteria, various MR imaging patterns and radiologic differential diagnosis of sporadic Creutzfeldt-Jakob disease are discussed in this article.
Aged ; Brain ; pathology ; Cerebral Cortex ; Cerebrospinal Fluid ; metabolism ; Creutzfeldt-Jakob Syndrome ; diagnostic imaging ; Dementia ; physiopathology ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; Electroencephalography ; Humans ; Hypoxia-Ischemia, Brain ; diagnostic imaging ; Male ; Prion Diseases ; physiopathology

The visual system plays an important role in our daily life. In this study, we found that loss of dendritic cell factor 1 (DCF1) in the primary visual cortex (V1) caused a sight deficit in mice and induced an abnormal increase in glutamic acid decarboxylase 67, an enzyme that catalyzes the decarboxylation of glutamate to gamma aminobutyric acid and CO, particularly in layer 5. In vivo electrophysiological recordings confirmed a decrease in delta, theta, and beta oscillation power in DCF1-knockout mice. This study presents a previously unknown function of DCF1 in V1, suggests an unknown contact between DCF1 and GABA systems, and provides insight into the mechanism and treatment of visual deficits.
Animals ; Brain Waves ; genetics ; Disease Models, Animal ; Electroencephalography ; Gene Expression Regulation ; drug effects ; genetics ; Geniculate Bodies ; drug effects ; metabolism ; Ginkgolides ; therapeutic use ; Glutamate Decarboxylase ; metabolism ; Lactones ; therapeutic use ; Membrane Proteins ; deficiency ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins ; deficiency ; genetics ; Photic Stimulation ; Proto-Oncogene Proteins c-fos ; metabolism ; Vision Disorders ; drug therapy ; genetics ; pathology ; physiopathology ; Visual Cortex ; metabolism ; pathology ; gamma-Aminobutyric Acid ; metabolism

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The finding that cellular microparticles (MPs) generated by injured cells profoundly impact on pathological courses of TBI has paved the way for new diagnostic and therapeutic strategies. MPs are subcellular fragments or organelles that serve as carriers of lipids, adhesive receptors, cytokines, nucleic acids, and tissue-degrading enzymes that are unique to the parental cells. Their sub-micron sizes allow MPs to travel to areas that parental cells are unable to reach to exercise diverse biological functions. In this review, we summarize recent developments in identifying a casual role of MPs in the pathologies of TBI and suggest that MPs serve as a new class of therapeutic targets for the prevention and treatment of TBI and associated systemic complications.
Animals ; Astrocytes ; metabolism ; pathology ; Biological Transport ; Blood Coagulation Factors ; genetics ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Injuries, Traumatic ; genetics ; metabolism ; pathology ; physiopathology ; Cell-Derived Microparticles ; chemistry ; metabolism ; pathology ; Cytokines ; blood ; genetics ; Disease Models, Animal ; Disseminated Intravascular Coagulation ; genetics ; metabolism ; pathology ; physiopathology ; Gene Expression Regulation ; Humans ; Microglia ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Signal Transduction

BACKGROUNDAmyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model.

METHODSThe 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1-42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence.

RESULTSIn 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1-42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation.

CONCLUSIONSoAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.

Alzheimer Disease ; metabolism ; physiopathology ; Amyloid Precursor Protein Secretases ; genetics ; metabolism ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; metabolism ; Animals ; Aspartic Acid Endopeptidases ; genetics ; metabolism ; Brain ; metabolism ; physiopathology ; Cells, Cultured ; Cellular Senescence ; genetics ; physiology ; Cognition ; physiology ; Cognition Disorders ; metabolism ; physiopathology ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons ; metabolism ; pathology ; Real-Time Polymerase Chain Reaction

OBJECTIVETo study the effects of Bushen Yisui Capsule (, BSYSC) on the oligodendrocyte lineage genes (Olig) 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE) in order to explore the remyelination effect of BSYSC.

METHODSThe mice were randomly divided into normal control (NC), EAE model (EAE-M), prednisone acetate (PA, 6 mg/kg), BSYSC high-dose (3.02 g/kg) and BSYSC low-dose (1.51 g/kg) groups. The mice were induced by immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55. The neurological function scores were assessed once daily. The pathological changes in mice brains were observed with hematoxylin-eosin (HE) staining and transmission electron microscope (TEM). The protein expressions of myelin basic protein (MBP), Olig1 and Olig2 in brains were measured by immunohistochemistry. The mRNA expressions of Olig1 and Olig 2 was also determined by quantitative real-time polymerase chain reaction.

RESULTSCompared with the EAE-M mice, (1) the neurological function scores were significantly decreased in BSYSC-treated mice on days 22 to 40 (P<0.01); (2) the inflammatory cells and demyelination in brains were reduced in BSYSC-treated EAE mice; (3) the protein expression of MBP was markedly increased in BSYSC-treated groups on day 18 and 40 respectively (P<0.05 or P<0.01); (4) the protein expression of Olig1 was increased in BSYSC (3.02 g/kg)-treated EAE mice on day 40 (P<0.01). Protein and mRNA expression of Olig2 was increased in BSYSC-treated EAE mice on day 18 and 40 (P<0.01).

CONCLUSIONThe effects of BSYSC on reducing demyelination and promoting remyelination might be associated with the increase of Olig1 and Olig2.

Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Brain ; drug effects ; pathology ; ultrastructure ; Bromodeoxyuridine ; metabolism ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Encephalomyelitis, Autoimmune, Experimental ; drug therapy ; genetics ; pathology ; physiopathology ; Female ; Fluorescent Antibody Technique ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; metabolism ; Nerve Tissue Proteins ; genetics ; metabolism ; Oligodendrocyte Transcription Factor 2 ; RNA, Messenger ; genetics ; metabolism

Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.
Animals ; Brain Injuries/pathology* ; Cerebral Cortex/physiopathology* ; Chemokine CCL2/metabolism* ; Chemokines, CC/metabolism* ; Hypoxia-Ischemia, Brain/metabolism* ; Macrophage Inflammatory Proteins/metabolism* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2/metabolism*

OBJECTIVETo investigate the effect of γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l -alanyl]-S-phenylglycine t-butyl ester, DAPT) on hyperoxia-induced brain white matter injury in mice.

MWTHODSThree-day-old C57BL/10J mouse pups were divided into air control (C) group, control+DAPT (10 mg/kg, injected intraperitoneally) group, hyperoxia group (exposed to 80% oxygen for 48 h), and hyperoxia+DAPT group. The brain and body weights of the mice were measured at postnatal days 3, 5, 12, and 28. Real-time PCR was used to detect Notch intracellular domain (NICD) mRNA expression in the brain after modeling, and the expressions of NG2 and myelin basic protein (MBP) were detected by double-labeled immunofluorescence assay to verify the oligdendrocycle type at postnatal day 12. The mice in each group were bred until postnatal day 28 for Morris water maze test.

RESULTSThe brain and body weights were significantly decreased in mice in hyperoxia group compared to the control mice, but increased significantly after DAPT treatment (P<0.05). Real-time PCR showed that a 48-hour hyperoxia exposure significantly increased NICD mRNA expression in the brain (P<0.05), which was decreased by co-treatment by DAPT (P<0.05). Hyperoxia also resulted in enhanced NG2 expression and lowered MBP expression in the brain (P<0.05). Compared with the control mice, the mice exposed to hyperoxia showed prolonged escape latency (P<0.05) and spent less time in the target quadrant with a lowered number of passing through the virtual platform (P<0.05). All these parameters were significantly improved by co-treatment with DAPT.

CONCLUSIONSpecific inhibition of Notch signaling pathway activation in the brain by the γ-secretase inhibitor DAPT can ameliorate white matter injury and learning and memory impairment in newborn mice with hyperoxia exposure.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Animals ; Body Weight ; Brain ; metabolism ; pathology ; Dipeptides ; pharmacology ; Hyperoxia ; physiopathology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Organ Size ; Receptors, Notch ; metabolism ; Signal Transduction ; White Matter ; pathology

BACKGROUNDMorbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.

METHODSForty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM). VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR) was initiated. Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE), and S100β were quantified with an enzyme-linked immunosorbent assay.

RESULTSCompared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01) and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01) with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01). The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01). Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01). Higher serum biomarkers of brain damage (NSE, S100β) were found in ACA than VFCA after resuscitation (P < 0.01).

CONCLUSIONSCompared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.

Animals ; Asphyxia ; complications ; physiopathology ; Brain ; metabolism ; Cardiopulmonary Resuscitation ; Heart Arrest ; metabolism ; pathology ; therapy ; Positron-Emission Tomography ; Swine ; Ventricular Fibrillation ; metabolism ; pathology ; therapy