Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

<p>Abstract</p> <p>Background</p> <p>Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia.</p> <p>Results</p> <p>Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals.</p> <p>Conclusion</p> <p>These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.</p

Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

Metabolites of 2-deoxyglucose in rat brain at 12-24 h: bounds on kinetic constants

Activities of 2-deoxy-D-glucose and its metabolites in rat brain were examined at 12, 16, 20, and 24 h after intraperitoneal injection of C-labeled 2-deoxy-D-glucose. Plasma radioactivity was monitored for 2 h before each of these determinations. As proportion of total brain radioactivity, 2-deoxy-D-glucose decreased monotonically from the unexpectedly high value of 22% at 12 h to 11% at 24 h after injection, 2-deoxy-D-glucose 6-phosphate decreased monotonically from 69% at 12 h to 23% at 24 h, and unphosphorylated products (of high and low molecular weight) increased from 10% at 12 h to 64% at 24 h. The data were analyzed in terms of a four-compartment model. Secure lower and upper bounds on the rate constant, k(*), for the dephosphorylation of 2-deoxy-D-glucose 6-phosphate were established: k(*) was at least 0.0158 ± 0.0014·min and at most 0.0385 ± 0.0037·min. If k(*) is constant in time, then appreciable dephosphorylation occurs within the 45-min experimental period commonly used in the standard 2-deoxy-D-glucose method for estimating local cerebral glucose utilization. The possibility that the effective k(*) is lower at such early times is reviewed in the light of a reanalysis of previously published data. Implications of these results for the 2-deoxy-D-glucose method are discussed from the points of view of numerical analysis and capillary heterogeneity