Effect of N-arachidonoyl-l-serine on human cerebromicrovascular endothelium

AbstractN-arachidonoyl-l-serine (ARA-S) is an endogenous lipid, chemically related to the endocannabinoid, N-arachidonoyl ethanolamine (i.e., anandamide) and with similar physiologic and pathophysiologic functions. Reports indicate that ARA-S possesses vasoactive and neuroprotective properties resembling those of cannabinoids. However, in contrast to cannabinoids, ARA-S binds weakly to its known classical receptors, CB1 and CB2, and is therefore considered to be a ‘cannabinoid-like’ substance. The originally described ARA-S induced-endothelial-dependent vasorelaxation was not abrogated by CB1, CB2 receptor antagonists or TRPV1 competitive inhibitor. The present report demonstrates that ARA-S enhances the fluorescence staining of both cannabinoid receptors (CB1 and CB2) in human brain endothelial cells (HBEC). This reaction is specific since it was reduced by respective selective receptor antagonist (SR141716A and SR141728A). ARA-S alone or in the presence of ET-1 was shown to alter the cytoskeleton (actin). Both ARA-S stimulated phosphorylation of various kinases (MAPK, Akt, JNK and c-JUN) and alteration of cytoskeleton are mediated via CB1, CB2 and TRPV1 receptors. The findings also showed the involvement of Rho/Rock and PI3/Akt/NO pathways in the ARA-S-induced phosphorylation of kinases and actin reorganization in HBEC. All of the above mentioned ARA-S-induced effects were reduced by the treatment with LY294002 (inhibitor of PI3/Akt kinase), except MAPK kinase. In addition, MAPK, JNK, c-JUN phosphorylation were inhibited by H1152 (inhibitor of Rho/ROCK kinase), except Akt kinase. Furthermore, PI3/Akt pathway was inhibited by pretreatment with l-NAME (inhibitor of NOS). The findings suggest that ARA-S is a modulator of Rho kinase and may play a critical role in the regulation of its activity and subsequent effects on the cytoskeleton and its role in supporting essential cell functions like vasodilation, proliferation and movement

Infarction of the entire corpus callosum as a complication in subarachnoid hemorrhage: A case report

The corpus callosum is the major commissural pathway connecting the cerebral hemispheres. This pathway receives its blood supply from anterior communicating artery, pericallosal artery, and posterior pericallosal artery. However, in some cases, the entire corpus callosum is supplied by median callosal artery; thus, occlusion of this artery can lead to infarction of the entire corpus callosum. Few reports have described this type of infarction, and no reports after subarachnoid hemorrhage (SAH) exist. Here, we report on a 42-year-old female who was diagnosed with SAH after two aneurysms were discovered in bifurcation of left anterior cerebral artery (A1-A2). After successful clipping was performed, the patient was alert and had no neurological deficits; moreover, the computed tomography images that were acquired after the operation showed no evidence of infarction. Nine days after admittance to the hospital, drowsiness and weakness of the left limbs with brain swelling appeared and decompressive hemi-craniectomy was performed. Diagnostic cerebral angiography revealed vasospasms in both anterior and middle cerebral arteries, thus fasudil hydrochloride was administered intra-arterially. While blood flow in all arteries improved, diffusion-weighted magnetic resonance imaging detected infarction along the entire length of the corpus callosum and in the medial region of the right frontal lobe. We believe this infarction was due to secondary ischemia of median callosal artery. This case reminded us of the anatomical variation wherein median callosal artery is the sole blood supply line for the corpus callosum and demonstrated that infarction of the entire corpus callosum is possible

Photoproduction of η-mesons off C and Cu Nuclei for Photon Energies below 1.1 GeV(I. Nuclear Physics)

The η-meson photoproduction cross sections have been measured on C and Cu targets for photon energies between 600 and 1100MeV to investigate the behavior of the S_11 (1535) resonance in a nucleus. The excitation functions of the cross section as well as angular and momentum distributions of η-mesons are in quantitative agreement with Quantum Molecular Dynamics (QMD) model calculations, in which the η-meson emission processes other than the S_11 (1535) resonance are also incorporated as proposed in the η-MAID model. It is shown that the excitation of the D_15 (1675) resonance might play an important role for E_γ>900MeV