Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.
Animals ; Brain Ischemia ; Cyclic AMP ; Cyclooxygenase 2 ; Diabetes Mellitus, Type 2 ; Down-Regulation ; Glucagon* ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Hyperglycemia ; Infarction, Middle Cerebral Artery ; Insulin ; Mice ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Oxidative Stress ; Phosphotransferases ; Rats ; Reperfusion Injury ; Second Messenger Systems ; Stroke*

Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60.51% in infarct volume. Postconditioning increased phospho-Akt (p-Akt) levels and NF-κB translocation to the nucleus as early as 1 h after tMCAO and oxygen-glucose deprivation. Furthermore, inhibition of Akt by Akt inhibitor IV decreased NF-κB promoter activity after postconditioning. Immunoprecipitation showed that interactions between TLR5, MyD88, and p-Akt were increased from postconditioning both in vivo and in vitro. Similar to postconditioning, flagellin, an agonist of TLR5, increased NF-κB nuclear translocation and Akt phosphorylation. Our results suggest that postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathways via TLR5 after cerebral ischemia. Additionally, the TLR5 agonist flagellin can simulate the neuroprotective mechanism of postconditioning in cerebral ischemia.
Animals ; Brain ; Brain Ischemia* ; Flagellin ; Immunoprecipitation ; In Vitro Techniques ; Infarction, Middle Cerebral Artery ; Mice* ; Neuroprotection ; Neuroprotective Agents ; NF-kappa B ; Phosphorylation ; Toll-Like Receptor 5

Crossed cerebellar diaschisis (CCD) is known to be due to a contralateral supratentorial lesion decreasing blood flow and the metabolism in a cerebellar hemisphere. Arterial spin labeling (ASL) is an imaging technique that utilizes arterial blood water as a tracer for quantifying the regional cerebral blood flow in magnetic resonance imaging (MRI). This case was a patient with simple partial status epilepticus (SPSE) and CCD confirmed by ASL-perfusion MRI. Controlling the SPSE resulted in improvement of CCD being observed in the follow-up ASL-perfusion MRI.
Cerebrovascular Circulation ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging* ; Metabolism ; Perfusion* ; Status Epilepticus* ; Water

Artemisia annua is a wormwood. Because it may induce Cytochrome P450 2C19 enzyme, Artemisia annua may have an influence on antiepileptic drugs which are substrates for the enzyme. This influence may negatively affect seizure control of epilepsy patient. We present a patient whose seizures were induced by Artemisia annua, despite he was taking levetiracetam which is not a substrate for the hepatic enzyme. Therefore there would be another mechanism of seizure induction of Artemisia annua besides hepatic metabolism.
Anticonvulsants ; Artemisia ; Artemisia annua* ; Cytochrome P-450 Enzyme System ; Epilepsy* ; Humans ; Metabolism ; Seizures*

Peptide mass mapping is the matching of experimentally generated peptides masses with the predicted masses of digested proteins contained in a database. To identify proteins by matching their constituent fragment masses to the theoretical peptide masses generated from a protein database, the peptide mass fingerprinting technique is used for the protein identification. Thus, it is important to know the theoretical mass distribution of the database. However, few researches have reported the peptide mass distribution of a database. We analyzed the peptide mass distribution of non-redundant protein sequence database in the NCBI after digestion with 15 different types of enzymes. In order to characterize the peptide mass distribution with different digestion enzymes, a power law distribution (Zipfs law) was applied to the distribution. After constructing simulated digestion of a protein database, rank-frequency plot of peptide fragments was applied to generalize a Zipfs law curve for all enzymes. As a result, our data appear to fit Zipfs law with statistically significant parameter values.
Databases, Protein* ; Dermatoglyphics ; Digestion ; Jurisprudence ; Peptide Fragments ; Peptides