We present a catheter-based optical diffusion and fluorescence(ODF)probe to study the functional changes of the brain in vivo.This ODF probe enables the simultaneous detection ofthe multi-wavelength absorbance and fl...We present a catheter-based optical diffusion and fluorescence(ODF)probe to study the functional changes of the brain in vivo.This ODF probe enables the simultaneous detection ofthe multi-wavelength absorbance and fluorescence emission from the living rat brain.Our previous studies,including a transient stroke experiment of the rat brain as well as the brainresponse to cocaine,have established the feasibility of simultaneously determining changes incerebral blood volume(CBV),tissue oxygenation(StO2)and intracellular calcium([Ca^(2+)]i,using the fluorescence indicator Rhod2).Here,we present our preliminary results of somatosensory response to electrical forepaw stimulation obtained from the rat cortical brain by using theODF probe,which indicate that the probe could track brain activation by directly detecting[Ca^(2+)]i along with separately distinguishing CBV and StO2 in real time.The changes of CBV,StO2 and[Ca^(2+)]i are comparable with the blood-oxygen-level-dependent(BOLD)response tothe stimulation obtained using functional magnetic resonance imaging(fMRI).However,thehigh temporal resolution of the optical methodology is advanced,thus providing a new modalityfor brain functional studies to understand the hemodynamic changes that underlie the neuronalactivity.展开更多
Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is ne...Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.展开更多
基金NIH Grants K25-DA021200,Laboratory Directed Research Development(LDRD)Grant(04-066)of Brook-haven National Laboratory,and by Department of Energy Office of Science and Biological Research.
文摘We present a catheter-based optical diffusion and fluorescence(ODF)probe to study the functional changes of the brain in vivo.This ODF probe enables the simultaneous detection ofthe multi-wavelength absorbance and fluorescence emission from the living rat brain.Our previous studies,including a transient stroke experiment of the rat brain as well as the brainresponse to cocaine,have established the feasibility of simultaneously determining changes incerebral blood volume(CBV),tissue oxygenation(StO2)and intracellular calcium([Ca^(2+)]i,using the fluorescence indicator Rhod2).Here,we present our preliminary results of somatosensory response to electrical forepaw stimulation obtained from the rat cortical brain by using theODF probe,which indicate that the probe could track brain activation by directly detecting[Ca^(2+)]i along with separately distinguishing CBV and StO2 in real time.The changes of CBV,StO2 and[Ca^(2+)]i are comparable with the blood-oxygen-level-dependent(BOLD)response tothe stimulation obtained using functional magnetic resonance imaging(fMRI).However,thehigh temporal resolution of the optical methodology is advanced,thus providing a new modalityfor brain functional studies to understand the hemodynamic changes that underlie the neuronalactivity.
基金supported by a grant from the Guangdong Science&Technology Plan Program in China,No.2014A020212043the a grant from the Shenzhen Science&Technology Plan Program in China,No.JCYJ20140414170821242+1 种基金the a grant from Shenzhen Collaborative Innovation Plan Program in China,No.GJHZ20120614154914623a grant from the Science&Technology Project of Shanxi Health and Family Planning Commission in China,No.201201060
文摘Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.
