Stroke upregulates TNFalpha transport across the blood-brain barrier. Export

@article{pan06stroke, abstract = {To determine how cytokine transport systems at the blood-brain barrier (BBB) participate in stroke progression and recovery, we generated a mouse model of transient middle cerebral artery occlusion (tMCAO). After 1 h of occlusion followed by nearly complete reperfusion, the neurological deficits lasted more than a week as shown by several behavioral tests. Despite the prominent infarct area indicated by reduced cerebral perfusion and confirmed by vital staining, the volume of distribution of (131)I-albumin in various brain regions was not significantly altered over time (12 h to 14 days). In sharp contrast, the blood-to-brain permeation of 125I-TNFalpha was significantly increased 5 days after tMCAO. Furthermore, excess unlabeled TNFalpha abolished this enhanced 125I-TNFalpha uptake. Thus, not only did the known saturable transport system for TNFalpha persist, but it functioned at a higher capacity in tMCAO mice. Upregulation of TNFR1 and TNFR2 partially explains the increased transport, as mRNA for both receptors showed the most pronounced increase (15-fold and 30-fold, respectively) in the ischemic hemisphere 5-7 days after tMCAO. However, even in the hemisphere contralateral to the ischemia induced by stroke, there was increased TNFalpha transport. The bilateral increase in 125I-TNFalpha entry from blood to brain suggests that TNFalpha trafficking in cerebral endothelial cells is influenced by global mediators in addition to the transporting receptors. Given the known multiple modulatory effects of TNFalpha after stroke, the results indicate that the TNFalpha transport system at the BBB facilitates neuroplasticity and plays an important role in stroke recovery.}, address = {Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. weihong.pan@pbrc.edu}, author = {Pan, W. and Ding, Y. and Yu, Y. and Ohtaki, H. and Nakamachi, T. and Kastin, A. J.}, citeulike-article-id = {1971236}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.expneurol.2005.11.020}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16412421}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16412421}, doi = {10.1016/j.expneurol.2005.11.020}, issn = {0014-4886}, journal = {Exp Neurol}, keywords = {alpha, bbb, tnf}, month = {March}, number = {1}, pages = {222--233}, posted-at = {2007-11-24 09:08:40}, priority = {2}, title = {Stroke upregulates TNFalpha transport across the blood-brain barrier.}, url = {http://dx.doi.org/10.1016/j.expneurol.2005.11.020}, volume = {198}, year = {2006} }

TY - JOUR ID - pan06stroke L3 - citeulike-article-id:1971236 N2 - To determine how cytokine transport systems at the blood-brain barrier (BBB) participate in stroke progression and recovery, we generated a mouse model of transient middle cerebral artery occlusion (tMCAO). After 1 h of occlusion followed by nearly complete reperfusion, the neurological deficits lasted more than a week as shown by several behavioral tests. Despite the prominent infarct area indicated by reduced cerebral perfusion and confirmed by vital staining, the volume of distribution of (131)I-albumin in various brain regions was not significantly altered over time (12 h to 14 days). In sharp contrast, the blood-to-brain permeation of 125I-TNFalpha was significantly increased 5 days after tMCAO. Furthermore, excess unlabeled TNFalpha abolished this enhanced 125I-TNFalpha uptake. Thus, not only did the known saturable transport system for TNFalpha persist, but it functioned at a higher capacity in tMCAO mice. Upregulation of TNFR1 and TNFR2 partially explains the increased transport, as mRNA for both receptors showed the most pronounced increase (15-fold and 30-fold, respectively) in the ischemic hemisphere 5-7 days after tMCAO. However, even in the hemisphere contralateral to the ischemia induced by stroke, there was increased TNFalpha transport. The bilateral increase in 125I-TNFalpha entry from blood to brain suggests that TNFalpha trafficking in cerebral endothelial cells is influenced by global mediators in addition to the transporting receptors. Given the known multiple modulatory effects of TNFalpha after stroke, the results indicate that the TNFalpha transport system at the BBB facilitates neuroplasticity and plays an important role in stroke recovery. IS - 1 JF - Exp Neurol SN - 0014-4886 AD - Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. weihong.pan@pbrc.edu EP - 233 TI - Stroke upregulates TNFalpha transport across the blood-brain barrier. VL - 198 SP - 222 KW - alpha KW - bbb KW - tnf AU - Pan, W AU - Ding, Y AU - Yu, Y AU - Ohtaki, H AU - Nakamachi, T AU - Kastin, AJ PY - 2006/03// UR - http://dx.doi.org/10.1016/j.expneurol.2005.11.020 ER -