新生仔期羊における低酸素血症時の脳血流に果たす末梢化学受容器の役割

The response of cerebral blood flow (CBF) during isocapnic hypoxic hypoxia was studied in 1-7 day old lambs that underwent sinoaortic chemodenervation. Lambs were anesthetized with pentobarbital and studied during moderate (arterial O2 content [CaO2] =10 vol %) and severe (CaO2 =6 vol %) hypoxic hypoxia. Regional brain blood flows were measured with the radioactive microsphere technique. Cerebral oxygen consumption (CMRO2) was calculated as the product of forebrain blood flow and the difference in oxygen content between arterial and sagittal sinus blood. Lambs were then subjected to either sham surgery (n=6) or to carotid chemodenervation and cervical vagotomy (n=6). Chemodenervation was verified by abolition of the transient increase in blood pressure following intravenous injection of sodium cyanide in intact subjects. Neither sham surgery nor chemodenervation had any effect on CBF or CMRO2 during hypoxic hypoxia. These data show that arterial chemoreceptors have no role in the regulation of cerebral vascular tone during hypoxic hypoxia in the 1-7 day old anesthetized lamb

BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development

AbstractBAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria. Here we evaluate the function of BAK in several mouse models of neuronal injury including neuronotropic Sindbis virus infection, Parkinson's disease, ischemia/stroke, and seizure. BAK promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. BAK protects neurons from excitotoxicity and virus infection in the hippocampus. As mice mature, BAK is converted from anti- to pro-death function in virus-infected spinal cord neurons. In addition to regulating cell death, BAK also protects mice from kainate-induced seizures, suggesting a possible role in regulating synaptic activity. BAK can alter neurotransmitter release in a direction consistent with its protective effects on neurons and mice. These findings suggest that BAK inhibits cell death by modifying neuronal excitability

Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia

No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research

Advances in translational medicine 2010

A.M.P. receives funding from the Spanish Ministry of Science and Innovation (SAF2008-04515-C01) and by the European Community (FP7/2007-2013; grant agreement number 201024). R.J.T. acknowledges funding from NIH/NINDS R01 NS046072.Peer Reviewe