The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia. 相似文献
The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms.
One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors.
Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere
with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent
increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked
by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine
also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into
a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to
32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression
in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically
relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic
neurons susceptible to the neurotoxicity associated with Alzheimer’s disease. 相似文献
Background: Only limited data exist comparing differences in sensory function and responses to neural blockade in infant and adult rats. Therefore, the authors sought (1) to compare baseline thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats; and (2) to compare the effects of sciatic nerve blockade on thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats.
Methods: Infant, adolescent, and adult rats were evaluated for proprioceptive, thermal, and mechanical nociceptive and motor function before and after sciatic blockade using a detailed neurologic examination.
Results: Mechanical and thermal nociception were present in all rats, starting from age 1 day. The withdrawal reflex latency to pinch was rapid at all ages, whereas that reaction to thermal stimulus depended on both age and temperature. In contrast, the tactile placing response and hopping response were absent at birth and developed completely during the first 10 days of life. The extensor postural thrust was absent in the first 2 weeks of life and developed variably during the first 50 days of life. Sciatic blockade duration is shorter in infant rats than in adult rats receiving the same dose per kilogram. A brief halothane general anesthetic at the time of sciatic injection in infant or adult rats does not alter the duration of blockade. 相似文献
The anterior part of Schistosoma japonicum cercaria is a specialized head organ which can slightly stretch out and retract. There are three different types of large unicellular glands in cercarial body, consisting of one head gland, 2 pairs of pre- and 3 pairs of postacetabular glands. These glands differ in position, gross feature, histochemistry and functions. Both polysaccharase and protease activities are demonstrated in the secretions from these glands. Mode of cercarial penetration is described in detail and the penetration is effected by a combination of lytic secretions and mechanical movements. The schematic representation of the process of cercarial penetration is presented. The dynamic distributions of schistosomula in skin at different time intervals after skin penetration in various mammalian hosts are shown. Some newly transformed schistosomula die while penetrating into the skin of 7 mammalian species and the mortality rate varies with the host species, and that can also be affected by the age of cercariae following emergence from the snail. Some physiological aspects between cercariae and newly transformed schistosomula are compared. In contrast to cercariae, schistosomula are saline-adapted and water-intolerant. They were modified histochemically and antigenically.
We have adapted the simple and sensitive McAb-antigen spot test (AST) for evaluating the efficacy of anti-Leishmania chemotherapy. Serum samples from 37 kala-azar patients were tested by McAb-AST, and all showed definite positive reactions before treatment. After a course of antimony treatment, 20 turned negative, coupled with the disappearance of clinical symptoms; another 12 cases responded with weak positivity accompanied by an improvement of clinical manifestations; and the remaining 5 antimony-resistant patients showed strong positive reactions, with their conditions gradually worsening. Furthermore, all 6 cases in which the diagnosis was missed by the bone marrow smear method turned McAb-AST negative after chemotherapy. These results suggest that McAb-AST can be used to evaluate the efficacy of chemotherapy as well as to avoid missed diagnosis by the bone marrow smear method. 相似文献