Effects of delayed ramelteon treatment on neurological function and tissue repair after cryogenic traumatic brain injury / 中国药理学通报

:Aim To study the effects of continuous dai¬ly administration of ramelteon starting at the subacute period of cryogenic traumatic brain injury (cTBI) on neurological function and brain tissue repair in mice. Methods Thirty male C57BL/6 mice were randomly divided into sham group, vehicle group and ramelteon treatment groups. The right sensory-motor cortex was damaged by pressing a copper probe precooled by liq¬uid nitrogen onto the skull. Ramelteon ( 10 nig 'kg-1 • d"1) was administered by gavage every day starting at different time points after cTBI (1 h, 1 d,3 d) until sacrifice on day 14. Beam walking test and open field test were used to evaluate the motor function. Toluidine blue staining was used to measure the infarct volume. Immunofluorescence was used to detect the expression of GAP-43 and synaptophysin in peri-infarct area. Mi¬croglia activation was detected using Iba-1. The area and thickness of glial scars were analyzed by detecting GFAP positive areas. Results All three treatment ( 1 h - 14 d, 1 - 14 d, and 3 - 14 d) significantly im¬proved cTBI induced motor dysfunction, reduced the infarct volume, elevated the expression of GAP -43 and synaptophysin, and decreased the area and thick¬ness of glial scar and microglia activation. In addition, all ramelteon treatment groups had similar effects on the above indexes. Conclusions Delayed ramelteon treatment can improve neurological dysfunction after cTBI,and the therapeutic time window can be delayed for up to three days after cTBI. Inhibiting glial scar formation and microglia activation, and promoting ax- onal regeneration and synaptogenesis may contribute to the beneficial effects of ramelteon.

Vasodilating effect of suberoylanilide hydroxamic acid on isolated thoracic aorta of rats and its mechanisms / 中国药理学通报

Aim To investigate the vasodilating effect of suberoylanilide hydroxamic acid ( SAHA) on isolated thoracic aorta of rats and the possible mechanisms. Methods Isolated thoracic aorta of rats were used to perfuse, and to observe the effect of accumulated concentration of SAHA (0.3, 1, 3, 10 and 30 p,mol • L_1) on isolated thoracic aorta at basal state, KC1 and NE precontracted state. At the same time, L-NAME, Indo, PMA and SP were used to explore its possible mechanisms of relaxing isolated thoracic aorta, and to investigate the role of the Ca2 during the vasodilating process. Results SAHA could relax KC1 and NE precontracted isolated thoracic aorta of rats (P <0. 01), and the effect on endothelium-intact was stronger than that on endothelium-denuded thoracic aorta (P < 0.01), but there was no significant effect on thoracic aorta at basal state. The vasodilatory effect of SAHA could be inhibited by L-NAME, Indo and PMA (P < 0.05), while that could be promoted by SP ( P < 0. 01). SAHA could attenuate vasoconstriction induced by CaCl2 and NE through inhibiting extracellular Ca2 + influxe and intracellular Ca2 release in a concentration-dependent manner ( P < 0. 01). Conclusions The vasodilating mechanisms of SAHA may be related to the increased production of vasodilatory factors NO and PGt2, and the inhibition of PKC, and the inhibition of extracellular Ca2 + influxe and intracellular Ca2 + release.

Effect of endogenous histamine on ischemic preconditioning induced cerebral ischemic tolerance / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of endogenous histamine on ischemic preconditioning induced cerebral ischemic tolerance in rats.</p><p><b>METHODS</b>Wild-type (WT) mice and histidine decarboxylase knock-out (HDC-KO) mice were preconditioned by bilateral carotid artery occlusion (BCCAO) for 6, 10,or 14 min and reperfused for 48 h,then subjected to permanent BCCAO and the survival time of WT and HDC-KO mice subjected to permanent BCCAO was observed. Histamine levels in the hypothalamus, hippocampus, striatum and cortex at 0.5 h,5 h or 48 h after 10 min BCCAO were determined with high-performance liquid chromatography.</p><p><b>RESULT</b>Ten minutes ischemic preconditioning significantly prolonged the survival time of WT mice subjected to permanent BCCAO. However,in HDC-KO mice, the ischemic tolerance was not induced with 10 min preconditioning. The histamine levels at 0.5 h or 48 h increased after 10 min preconditioning, but not at 5 h.</p><p><b>CONCLUSION</b>Endogenous histamine in brain may be an essential mediator in ischemic preconditioning induced cerebral ischemic tolerance.</p>

VEGF and central nervous system diseases / 浙江大学学报·医学版

Vascular endothelial growth factor (VEGF or VEGF-A) is a hypoxia induced angiogenic growth factor that is potent in neurotrophy,neuroprotection, anti-apoptosis and cell proliferation. Recent reports suggest that VEGF is related to many central nervous system diseases, such as cerebral ischemic disease, Alzheimer's disease and Parkinson's disease. Further study of the relationship between VEGF and central nervous system diseases,and investigation of VEGF related drugs will shed light on a new way for treatment of central nervous system diseases.