ABSTRACT
Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.
Subject(s)
Animals , Humans , Mice , Rats , Angiostrongylus cantonensis , Angiostrongylus , Apoptosis , Behavior Rating Scale , Caspase 3 , Caspase 8 , Central Nervous System , Cerebral Cortex , Diagnosis , Eosinophils , Gait , Gene Expression , Headache , Hippocampus , Meningitis , Meningoencephalitis , Neurons , Receptors, Tumor Necrosis Factor, Type I , RodentiaABSTRACT
Objective To investigate the effects of intestinal ischemia-reperfusion (I/R) on the brain in rats. Methods Sixty-four healthy male SD rats weighing 250-300 g were randomly allocated to one of 2 groups (n = 32 each): sham operation group (S) and intestinal I/R group (I/R). Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 90 min followed by reperfusion. Eight animals were sacrificed at each of the following time points: 2, 6, 12 and 24 h of reperfusion (T1-4) in each group. After a median sternotomyblood samples were taken from left ventricle for measurement of plasma TNF-α and IL-6 (by ELISA). Intestine and brain tissue was harvested for microscopic examination and detection of apoptosis ( by TUNEL). The cognitive function was tested using Morris water maze at 24 h. Results No abnormality was found in intestine and brain tissue in group S. Intestinal damage and neurodegeneration were detected in group I/R. Intestinal I/R significantly increased cerebral apoptosis in group I/R compared with group S. Plasma TNF-a and IL-6 concentrations were significantly higher at T1-4 in group I/R than in group S. The escape latency and swimming distance were significantly increased, while the number of crossing the platform was decreased in group I/R compared with group S. There was no significant difference in the swimming speed between the 2 groups. Conclusion Intestinal I/R can induce brain injury and lead to cognitive dysfunction. I/R-induced release of inflammatory mediators and neuronal apoptosis are involved in the underlying mechanism.
ABSTRACT
[Objective ] Intrastriatal Parr interneurons are considered to be the junction between striatal input and output neurons. This study purposes to confirm the morphology of Parr neurons and their distribution in striatum. [Method] Adult male SD rats were perfused and the brains were removed. The sections were conducted with a semiconductor-frozen microtome, then single labeling and double labeling were immunocytochemically conducted with PAP technique. Positive neurons were observed, counted, and calculated, and analyzed with SPSS. [Results] The distribution of Parr positive neurons in striatum was inhomogeueous, and was the most dense in the dorsal lateral area (P<0.001) ; the distribution of Parr positive neurons in matrix compartment was apparently more than patch compartment (82.0% vs 18.0%, P<0.001); Parr positive neurons in striaturn were medium-sized cell bodies with polygonal or oval in shape (mean diameter is 11.68 μm), and were larger in the lateral area than that in the medial area (P<0.01) ; the positive dendrites were dense and smooth without dendrite spines; the positive axons 1 were slender and their collaterals extended in striatum. [Conclusion] The characteristic of Parr positive neurons collecting mostly in lateral striatum and matrix eompartment, as well as their traits of intemeurons, indicated that they would affect the striatal projection neuronal function.
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AIM： To study the pathological relationship of vascular cell adhesion molecule-1 (VCAM-1) expression and monocyte/macrophage infiltration with focal brain ischemia. METHODS: Immunohistochemical technique and focal brain ischemia/reperfusion model were used in the study in order to explore profiles and time-course of VCAM-1 expression and monocyte macrophage (ED2 positive cell) infiltration in ischemic rat brain. RESULTS: VCAM-1 was up-regulated in microvascular endothelial cells in ischemic cortex at 1h postischemia, and continuously expressed during the time of reperfusion. ED2 positive cells infiltrated into ischemic cortex at 1h iscehmia/ 2h reperfusion and then ED2 positive cells increased gradually with the time of reperfusion, ED2 positive cell infiltration showed apparently relationship with VCAM-1 expression, and both of them exhibited the some changes of time-dependence. CONCLUSION: Cerebral ischemia induced VCAM-1 expression and ED2 positive cell infiltration and VCAM-1 may regulate the recruitment of ED2 positive cells in the ischemic brain region. The results suggested that VCAM-1 and ED2 positive cells may be participated in the pathogenesis of cerebral ischemic injury.
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AIM: To explore the expressive profile of nestin protein in the focal ischemic brain and to study the recovery mechanism of brain focal infarct . METHODS: Cellular morphology, time-course and distribution pattern of nestin positive response were immunohistochemically examined in different brain regions of 36 adult male SD rats. RESULTS: Nestin positive response of different brain regions in sham operated rats was present in small- and micro-vasculartures and the third ventricle bottom and ependyma. A large number of nestin positive cells were detected in ischemic brain, and were more remarkable in the cortical areas of parietal lobe and preoptic area as well as ischemic caudoputamen. Stellate nestin positive cells were located in the deep layer of ischemic cortex, but fibrillary cells were located in the shallow layer. Nestin positive cells in the ischemic caudoputamen showed the same changes of morphology as those cells in the deep layer of ischemic cortex. Morphological and number alterations of nestin positive cells were the most remarkable at 1 weeks post-ischemia, which showed more hypertrophy and proliferation in morphology, and a marked increase in number was present in the ischemic cerebral cortex and the ischemic caudoputamen. These alterations of nestin positive cells persisted up to 6 weeks post-ischemia, and then, the nestin positive response in the ischemic brain decreased gradually. CONCLUSION: Focal cerebral ischemia induces nestin re-expression on reactive astrocytes, which may be very important to the self-recovery of cerebral infarct.
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AIM: To study the pathological relationship of vascular cell adhesion molecule-1 (VCAM-1) expression and monocyte/macrophage infiltration with focal brain ischemia. METHODS: Immunohistochemical technique and focal brain ischemia/reperfusion model were used in the study in order to explore profiles and time-course of VCAM-1 expression and monocyte macrophage (ED2 positive cell) infiltration in ischemic rat brain. RESULTS: VCAM-1 was up-regulated in microvascular endothelial cells in ischemic cortex at 1h postischemia, and continuously expressed during the time of reperfusion. ED2 positive cells infiltrated into ischemic cortex at 1h iscehmia/ 2h reperfusion and then ED2 positive cells increased gradually with the time of reperfusion, ED2 positive cell infiltration showed apparently relationship with VCAM-1 expression, and both of them exhibited the some changes of time-dependence. CONCLUSION: Cerebral ischemia induced VCAM-1 expression and ED2 positive cell infiltration and VCAM-1 may regulate the recruitment of ED2 positive cells in the ischemic brain region. The results suggested that VCAM-1 and ED2 positive cells may be participated in the pathogenesis of cerebral ischemic injury.
ABSTRACT
AIM: To study the microglial/macrophagic reactions to chronic foral cerebral ischmeia METHODS:ED1 and OX42 positive cellular reactive profiles including time-course and distribution as well as morphological changes were explored in the ischemic cortex and the ischemic caudoputamen of 36 SD adult rats by using focal cerebral ischemic model and immunohistochemical method RESULTS: On the 3rd day after ischemia, an increased number of round ED1 positive cells were found in the outer boundary of cortical ischemic foci and the ischemic caudoputamen, and some of the positive cells were present in the cortical ischemic core At 2nd week after ischemia, ED1 positive cells peaked in number, and they were located at cortical ischemic core and lateral caudoputamen, at which they persisted up to 6 weeks after ischemia. On the 3rd day after ischemia, ramified OX42 positive cells became hypertrophy and a marked increase in number, and they were present at the periphery of ischemic foci and in the ischemic caudoputamen At 2nd week after ischemia, OX42 positive cells became more hypertrophy, and a number of round OX42 positive cells were detected in the cortical ischemic core, in which they persisted up to 6 weeks after ischemia. CONCLUSION:Focal cerebral ischemia induces microglial/macrophagic reaction persistently, which may be correlative with neuronal delayed injury and self recovery of ischemic foci.