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Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry 总被引:39,自引:0,他引:39
Englund U Bjorklund A Wictorin K Lindvall O Kokaia M 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(26):17089-17094
In vitro expanded neural stemprogenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry. 相似文献
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Kandelaki G Butsashvili M Kalandadze I Iosava M Avaliani N Imnadze P 《Acta tropica》2012,123(1):47-48
Malaria is well known in Georgia since ancient times, causing national disasters with associated significant mortality and economic losses. By 1970 Georgia managed to reach complete and sustained elimination of the disease as a result of comprehensive anti-malaria measures undertaken in the country. However from the mid-1990s, economic collapse following disintegration of Soviet Union causing breakdown of important public health networks including anti-malaria preventive and control infrastructure resulted in gradual increase of malaria cases in the country with a peak of 437 and 474 cases in 2001 and 2002, respectively. From 2000 two major anti-malaria efforts were carried out by National Center for Disease Control and Public Health, WHO and Global Fund to Fight AIDS, tuberculosis and malaria and as result of comprehensive and collaborative work in 2010 the level of zero cases of local mosquito-borne malaria transmission was achieved and the country entered the elimination phase. 相似文献
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Andreas T. Srensen Litsa Nikitidou Marco Ledri En-Ju D. Lin Matthew J. During Irene Kanter-Schlifke Merab Kokaia 《Experimental neurology》2009,215(2):328-333
Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy.Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how synaptic plasticity and transmission is affected by kindling and NPY overexpression by field recordings in CA1 stratum radiatum of brain slices. In animals injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected by rAAV-NPY treatment, and may be considered less critical for clinical application in epilepsy patients already experiencing memory disturbances. 相似文献
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Marco Ledri Andreas Toft Sørensen Ferenc Erdelyi Gabor Szabo Merab Kokaia 《Hippocampus》2011,21(2):198-211
Cholecystokinin (CCK)‐expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory‐forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65‐GFP transgenic mice for prospective identification of CCK basket cells and whole‐cell patch‐clamp recordings, we show for the first time that excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The frequency of spontaneous and miniature EPSCs, as well as the amplitudes of stimulation‐evoked EPSCs were decreased. Similarly, the frequency of both spontaneous and miniature IPSCs, and the amplitudes of stimulation‐evoked IPSCs were decreased after NPY application. Most of the effects of NPY could be attributed to a presynaptic site of action. Our data provide the first evidence that the excitatory and inhibitory inputs onto the CCK basket cells could be modulated by local levels of NPY, and may change the way these cells process extrahippocampal afferent information, influencing hippocampal function and its network excitability during normal and pathological oscillatory activities. © 2009 Wiley‐Liss, Inc. 相似文献
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Keshelava G Nachkepia M Arabidze G Janashia G Beselia K 《Annals of vascular surgery》2012,26(4):572.e15-572.e17
This article reports an unusual case of positional compression of internal carotid artery resulting in carotid thrombosis and stroke in a 37-year-old man. A patient was operated urgently for a free-floating thrombotic mass in the internal carotid artery. Open thrombectomy was performed in acute phase of stroke for prevention of the recapitulative cerebral thromboembolism. Hemiplegia completely disappeared within 7 months. 相似文献
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A brief period of rapidly recurring hippocampal seizures can lead to the progressive development of a permanent increase of seizure susceptibility over several weeks, so-called ‘delayed kindling'. We have analyzed seizure parameters critical for the induction of delayed kindling in two strains of rats characterized by fast and slow rates of traditional kindling, respectively. Forty seizures were produced during about 3 h by electrical kindling stimulations every 5 min in the ventral hippocampus. The fast rats displayed several generalized convulsions and had long periods of epileptiform activity, whereas the slow animals only exhibited brief, focal seizures. Changes in excitability were determined after 4 weeks using five test stimulations, and 2 weeks later by subjecting all animals to traditional hippocampal kindling. The fast rats showed clearly enhanced responsiveness at these time points, whereas no evidence of permanently increased seizure susceptibility was obtained in the slow rats. Our data indicate that the long-lasting stimulus-evoked seizures are mainly responsible for inducing delayed kindling, whereas the number of seizure events or generalized convulsions, and the total duration of epileptiform activity are less important. We hypothesize that long seizure episodes may be necessary to trigger the cascade of gene changes regulating the development of epilepsy. 相似文献
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Several lines of evidence indicate that neurotrophic factors (NTFs) could be key causal mediators in the development of acquired epileptic syndromes. Yet the trophic properties of NTFs indicate that they might be used to treat epilepsy-associated damage. Accordingly, different NTFs, or even the same NTF, could produce functionally contrasting effects in the context of epilepsy. Recent experimental evidence begins to shed light on the mechanisms underlying these contrasting effects. Understanding these mechanisms will be instrumental for the development of effective therapies, which must be based on a careful consideration of the biological properties of NTFs. Here, we critically evaluate new information emerging in this area and discuss its implications for clinical treatment. 相似文献
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