RESUMO
Integrins are heterodimeric transmembrane cell adhesion receptors that are essential for a wide range of biological functions via cell-matrix and cell-cell interactions. Recent studies have provided evidence that some of the subunits in the integrin family are involved in synaptic and behavioral plasticity. To further understand the role of integrins in the mammalian central nervous system, we generated a postnatal forebrain and excitatory neuron-specific knockout of alpha8-integrin in the mouse. Behavioral studies showed that the mutant mice are normal in multiple hippocampal-dependent learning tasks, including a T-maze, non-match-to-place working memory task for which other integrin subunits like alpha3- and beta1-integrin are required. In contrast, mice mutant for alpha8-integrin exhibited a specific impairment of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, whereas basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD) remained unaffected. Because LTP is also impaired in the absence of alpha3-integrin, our results indicate that multiple integrin molecules are required for the normal expression of LTP, and different integrins display distinct roles in behavioral and neurophysiological processes like synaptic plasticity.
Assuntos
Região CA1 Hipocampal/fisiologia , Integrinas/fisiologia , Aprendizagem/fisiologia , Potenciação de Longa Duração/genética , Animais , Região CA1 Hipocampal/crescimento & desenvolvimento , Feminino , Integrinas/deficiência , Integrinas/genética , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/metabolismo , Deficiências da Aprendizagem/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subunidades Proteicas/deficiência , Subunidades Proteicas/genética , Subunidades Proteicas/fisiologia , Transmissão Sináptica/genéticaRESUMO
SETTING: Tertiary referral centres. OBJECTIVE: To provide comprehensive updates on the aetiologies, angiographic findings and outcomes of bronchial artery embolisation (BAE) for life-threatening haemoptysis in Hong Kong. DESIGN: Retrospective review of clinical records of consecutive patients presenting with life-threatening haemoptysis from 2000 to 2006. RESULTS: There were 3006 admissions due to haemoptysis involving 2260 patients during the study period; of these, 251 patients had life-threatening haemoptysis. Pulmonary tuberculosis (PTB) (active or inactive) and bronchiectasis were the main underlying causes. BAE was attempted in 167 patients. There was a high prevalence of bilateral bronchial arterial abnormalities (31.7%), presence of abnormal non-bronchial arteries (41.3%) and presence of broncho-pulmonary shunt (38.9%). BAE had a high immediate success rate of 95.7%, with a 5-year recurrence rate of 45.0%. Recurrent life-threatening haemoptysis was independently associated with past history of haemoptysis (P = 0.024), presence of broncho-pulmonary shunt (P = 0.013), and incomplete embolisation (P = 0.002). Complications were uncommon (<5%) and self-limiting. CONCLUSIONS: In Hong Kong, about one tenth of admissions due to haemoptysis were life-threatening. PTB and bronchiectasis were the major causes. Complications due to BAE were uncommon and self-limiting, with super-selective catheters.