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 pathogenesis of acute brain ischemia is very complex, involving multiple mechanisms including excessive free radical generation. Oxidative stress means the imbalance between the generation and removal of free radicals. Once acute brain ischemia occurs, the reactive oxygen species interact with large numbers of biomacromolecules, irreversibly change or destroy the functions of cellular lipids, proteins, and nucleic acids, and thus initiate cell signaling pathways. However, the molecular biological characteristics of oxidative stress and the way to prevent and treat acute brain ischemia still need further investigations.
Brain Ischemia ; metabolism ; physiopathology ; Humans ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Signal Transduction

OBJECTIVETo explore the impacts of erythropoietin on vascular endothelial growth factor receptor 2 (VEGFR2) by the extracellular signal-regulated kinase (ERK) signaling pathway in a neonatal rat model of periventricular white matter damage.

METHODSAll of postnatal day 4 rats were randomized into three groups: the sham group [without hypoxia-ischemia (HI)], the HI group (HI with saline administration), and the erythropoietin (EPO) group [HI with recombinant human erythropoietin (rh-EPO) administration]. Rat pups underwent permanent ligation of the right common carotid artery, followed by 6% O2 for 2 hours or sham operation and normoxic exposure. Immediately after the HI, rats received a single intraventricular injection of rh-EPO (0.6 IU/g body mass) or saline. ERK and phosphorylation-ERK were examined at 60 minutes and 90 minutes after operation, and VEGFR2 were detected at 2 and 4 days after operation by using Western blot.

RESULTSAt 60 minutes and 90 minutes after operation, the proteins of phosphorylation-ERK were significantly higher in HI rats than in the sham rats and significantly higher in HI+EPO rats than in the HI rats (P<0.05). Two days after operation, VEGFR2 was not significantly different between sham and HI rats. However, the proteins of VEGFR2 were increased after administration of rh-EPO (P<0.05). Four days after operation, the proteins of VEGFR2 were significantly higher in HI rats than in the sham rats and significantly higher in HI+EPO rats than in the HI rats (P<0.05).

CONCLUSIONEPO may regulate VEGFR2 expression by affecting the intracranial ERK signaling pathways.

Animals ; Animals, Newborn ; Disease Models, Animal ; Erythropoietin ; pharmacology ; Humans ; Hypoxia-Ischemia, Brain ; physiopathology ; MAP Kinase Signaling System ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; White Matter ; physiopathology

OBJECTIVETo study the changes of miRNA expression in the pineal gland of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible roles of miRNA in the pathogenesis of circadian rhythm disturbance after HIBD.

METHODSSeven-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: HIBD and sham-operated. HIBD was induced according to the Rice-Vannucci method. The pineal glands were obtained 24 hours after the HIBD event. The expression profiles of miRNAs were determined using GeneChip technigue and quantitative real-time PCR (RT-PCR). Then the miRNA which was highly expressed was selected. The expression levels of the chosen miRNA were detected in different tissues (lungs, intestines, stomach, kidneys, cerebral cortex, pineal gland). RT-PCR analysis was performed to measure the expression profiles of the chosen miRNA and the targeted gene Clock mRNA in the pineal gland at 0, 24, 48 and 72 hours after HIBD.

RESULTSmiRNA-182 that met the criteria was selected by GeneChip and RT-PCR. miRNA-182 was highly expressed in the pineal gland. Compared with the sham-operated group, the expression of miRNA-182 was significantly up-regulated in the pineal gland at 24 and 48 hours after HIBD (P<0.05). Compared with the sham-operated group, Clock mRNA expression in the HIBD group increased at 0 hour after HIBD, decreased at 48 hours after HIBD and increased at 72 hours after HIBD (P<0.05).

CONCLUSIONSmiRNA-182 may be involved in the pathogenesis of circadian rhythm disturbance after HIBD.

Animals ; Animals, Newborn ; CLOCK Proteins ; genetics ; Circadian Rhythm ; physiology ; Female ; Gene Expression Regulation ; Hypoxia-Ischemia, Brain ; physiopathology ; Male ; MicroRNAs ; analysis ; physiology ; Pineal Gland ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

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*

To evaluate the regulating effect of Buyang Huanwu decoction and its simple prescription (Naojian tablet) on CDK4/Cyclin D1 expression in hippocampus tissues of rats with cerebral ischemia, SD rats were divided into the sham-operation group, the model group, the Buyang Huanwu decoction group (ig, 3.15 g · kg⁻¹) and the simple prescription group (ig, 2.41 g · kg⁻¹). Each group was further divided into five subgroups based on time points after the administration, i. e. 1 d, 3 d, 7 d, 14 d and 28 d, respectively. CDK4/Cyclin D1 expressions of the group at different time points were examined by using immunohistochemistry and real-time qPCR. According to the results, the cerebral ischemia model group showed higher CDK4/Cyclin D1 expression than the sham-operation groups (P < 0.05), suggesting that the cell cycle signal pathway would be activated by the cerebral ischemic injury. Both Buyang Huanwu decoction and simple prescription groups showed significantly lower cyclin expression than the model group at 3 d, 7 d, 14 d, 28 d (P < 0.05), indicating both Buyang Huanwu decoction and its simple prescription could play the neuroprotective effect through the cell cycle signal pathway.
Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Cycle ; drug effects ; Cyclin D1 ; genetics ; metabolism ; Cyclin-Dependent Kinase 4 ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of Buyang Huanwu Decoction (, BYHWD) on estradiol (E2) and estradiol receptor (ER) in serum and brain in ovariectomized rats after middle cerebral artery occlusion (MCAO).

METHODSAdult female rats were ovariectomized and focal cerebral ischemic was induced by MCAO. Rats were randomly divided into normal, ovariectomy (OVX), MCAO, OVX+MCAO, OVX+MCAO+E2, and OVX+MCAO+BYHWD group. Rats were administered BYHWD 5 g/kg daily, estradiol valerate 500 μg/kg per day or distilled water for 7 consecutive days. Neuronal function and infarct volume were measured on day 7 after artery occlusion, and E2 and ER concentration in serum and brain were checked by enzyme-linked immunosorbent assay.

RESULTSBYHWD significantly improved the neurological behavior, reduced the infarction volume, increased E2 concentration in serum and brain, and increased ER concentration in the brain in ovariectomized rats after MCAO.

CONCLUSIONThe neuroprotective effects of BYHWD are associated with estrogen and its receptor.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; drug therapy ; pathology ; physiopathology ; Cerebral Infarction ; complications ; drug therapy ; pathology ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estradiol ; blood ; Female ; Infarction, Middle Cerebral Artery ; complications ; drug therapy ; pathology ; physiopathology ; Ovariectomy ; Rats, Wistar ; Receptors, Estradiol ; blood

Nitric oxide (NO), which is involved in the regulation of the cardiovascular system, nervous system, immune system, reproductive system, digestive system and other physiological activities, is an important biological substance with activity. Under normal physiological conditions, neuronal nitric oxide synthase (nNOS) can precisely regulate the nervous system NO production, release, diffusion and inactivation processes. But an excess of NO associates with the development of cerebral ischemia, Alzheimer's and Parkinson's psychosis nervous system diseases, while inhibition of nNOS activity can regulate the content of NO in vivo, and produce a therapeutic effect on some of the nervous system diseases. This review mainly describes the structure and regulation of nNOS and recent developments of small molecule inhibitors of nNOS.
Alzheimer Disease ; physiopathology ; Brain Ischemia ; physiopathology ; Humans ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; antagonists & inhibitors ; metabolism ; Parkinson Disease ; physiopathology

OBJECTIVETo observe the effect of Huatuo Zaizao extractum (HTZZ) on focal cerebral ischemia/reperfusion (I/R) neurogenesis in rats induced by middle cerebral artery occlusion (MCAO) and its mechanism.

METHODTotally 55 healthy adult male Sprague-Dawley rats were divided into the sham operation group, the MCAO model group and HTZZ high, middle and low dose groups (5, 2.5, 1.25 g x kg(-1)), with 11 rats in each group, and orally administered with drugs. The focal cerebral ischemia model was established by performing a middle cerebral artery occlusion (MCAO, 90 min) followed by a seven-day reperfusion (once a day). The neurogenesis and expressions of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were detected by the immunofluorescent staining. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF).

RESULTMCAO (90 min) followed by a seven-day reperfusion resulted in the significant increase in the number of penumbra cortex newborn neurons (BrdU(+) -NeuN(+)), which was accompanied by the growth of ERK and CREB phosphorylation and VEGF and BDNF levels. HTZZ could promote the generation of newborn neurons (BrdU(+)-NeuN(+)) and the ERK and CREB phosphorylation and increase VEGF and BDNF levels at the ischemic side.

CONCLUSIONHTZZ could promote the neurogenesis, which may be the interventional targets of effective traditional Chinese medicine Huatuo Zaizao extractum in promoting the self-repair function of the cerebral ischemic areas.

Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Neurogenesis ; drug effects ; Neurons ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Vascular Endothelial Growth Factor A ; genetics ; metabolism