Establishment of an animal model of dural venous sinus embolism

BACKGROUND： The pathological mechanism of secondary brain lesion following an embolism remains unclear. The establishment of an animal model that imitates the clinical pathophysiological processes is crucial to better study this disease during a certain time window. OBJECTIVE： To establish a new animal model of dural venous sinus embolism that is simple, has a high success rate, and emulates the pathophysiological course of clinical disease. DESIGN, TIME AND SETTING： A randomized block design trial was performed at the Department of Anatomy, Ningxia Medical College between March and December 2007. MATERIALS： Fifty-eight healthy, adult, Sprague Dawley rats were used in the present study. Plastic emboli, with a total length of 0.4 cm, were self-made. Each plastic embolus had a conical anterior segment; the largest diameter being 0.12 cm. The posterior segment became gradually thin and flat, with a width of 0.2 cm and length of 0.1 cm. METHODS： The fifty-eight rats were randomly divided into three groups： control （n = 6）, embolism （n = 26）, and sham-embolism （n = 26） groups. In the embolism group, a solid embolus was slowly inserted and fixed into the posterior part of the superior sagittal sinus against the flow of blood. The posterior segment was detained outside the superior sagittal sinus for fixing. In the sham-embolism group, rats were subjected only to sinus sagittalis superior exposure. In the control group, rats received no treatments. In both the embolism and the sham-embolism groups, the rat brains were resected at 6 hours, 1, 3, and 5 days post-surgery. MAIN OUTCOME MEASURES： （1） Brain surface appearance in the embolism and sham-embolism groups. （2） Thrombosis in the embolism group. （3） Cerebrospinal fluid content in the above-mentioned two groups. RESULTS： In the embolism group, the model success rate was 92% （24/26）. There was visible thrombosis in the superior sagittal sinus. Cerebral edema was noticeable under a microscope. These changes were visible at 6 hours after embolism and were most obvious at 1 day after surgery. In the embolism group, cerebrospinal fluid content reached a peak level at 6 hours post-surgery and was significantly increased compared with the sham-embolism and the control groups （P 〈 0.05）. At 1 day post-surgery, the amount of cerebrospinal fluid was still greater in the embolism group compared to the control group （P 〈 0.05） CONCLUSION： The method of inserting a solid embolus has many benefits, such as being able to directly observe, short cycle time, and minimal wound. The detained posterior segment prevents movement and perfusion of embolus, which results in a high success rate.

Down-regulation of N-methyl-D-aspartate receptor subunits 1 affects neurogenesis of hippocampal neural stem cells

Schizophrenia is a common and serious mental illness characterized by severe impairments in thinking,emotions,and behaviors.Usually,the cognitive deficits of schizophrenia are closely associated with abnormal neurogenesis due to the hypofunction of certain neural receptors such as N-methyl-D-aspartate receptors(NMDARs),which mediates neurotransmission.However,little is known about the involvement of NMDAR1 in regulating hippocampal neurogenesis in schizophrenia.In the current study,we present evidence suggesting that NMDAR1 regulates hippocampal neurogenesis as lentivirus-mediated shRNA silencing NMDAR1 gene or blocking with MK-801 results in abnormal neurogenesis consistently found in schizophrenia.The important finding was clearly demonstrated by the multiparametric assessments,including morphology,immunofluorescence,western blotting,and flow cytometry.Simultaneously,our results indicated that knockdown and blockade of NMDAR1 significantly attenuated the proliferation of hippocampal neural stem cells(hNSCs)and decreased the differentiation to neurons.More importantly,the blockade of NMDAR1 with MK-801 aggravated the apoptosis of hNSCs.Thus,it is likely that NMDAR1 functions as a new target for the treatment of schizophrenia.Our present study may provide a novel insight for further investigation of the pathogenesis of schizophrenia.