RESUMO
The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.
RESUMO
The key factor of chemotherapy for brain disorders is to penetrate brain blood barrier(BBB). Receptor mediated en-docytosis is one of the mechanisms for drug carriers to cross the BBB. Angiopep-2(ANG)can specifically bind to low density lipopro-tein receptor-related proteins 1(LRP-1)overexpressed on BBB and glioma cells,thus exhibits a higher LRP-mediated BBB penetra-tion capability. Its targeting efficiency is higher than that of other targeting molecules such as transferrin and(TF)lactoferrin(LF). This paper introduces the structure and function of ANG,and its application in brain targeting delivery systems,in order to provide references for research and development of brain targeting preparations and guidance for therapy of brain diseases.
RESUMO
Objective To investigate the expressions of Occludin in brain after bacterial meningitis and to discuss possible molecular mechanism of bacterial meningitis when brain edema occurs. Methods The models of bacterial meningitis and normal control were constructed via inoculating intracisternally with strain Ⅲ streptococcus pneumoniae and the same volume of normal saline solution, respectively. The expression of Occludin in brain was detected by immunohistochemistry and Western blot methods respectively and 24 h, 48 h and 5 days after inoculation. Results (1) Loeffler neurologic deficit score (NDS) in 24 h, 48 h and 5 d decreased significantly when compared with that of control group (P < 0.05). (2) After the brain received streptococcus pneumoniae injection, expression of Occludin began to decrease at 24 h and touch the bottom at 48 h,then increase at the 5th day, but still remained lower than that in control group, which indicated statistical difference (P < 0.05). Conclusions Expression of Occludin in the models of bacterial meningitis decreased firstly and then increased regularly. It suggests that Occludin plays a protective role during the development of infectious brain edema.
RESUMO
The effect of high dos; dexamethasone(5mg/kg wt, intravenous injection)to prevent and treat the secondary pathological damage of craniocerebral injury was studied in animal models of craniocerebral injury caused by high-velocity missiles in dogs.We observed ths physiological changes, analyzed the value of serum and. cerebrospinal fluid lactate dehydrogenase, estimated the permeability of blood brain barrier (BBB) and studied brain pathology by light and electron microscopy.The results suggest high dose dexamethasone can help to restore ths structure and function of BBB, protect brain cells as well as lessai the secondary pathological damage in tha respiratory and circulatory systems and reduce th production of lipoptrox-ides(LPO).