C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model.
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C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model. / Thundyil, John; Pavlovski, Dale; Hsieh, Yu-Hsuan; Gelderblom, Mathias; Magnus, Tim; Fairlie, David P; Arumugam, Thiruma V.
In: NEUROMOL MED, Vol. 14, No. 1, 1, 2012, p. 30-39.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - C5a receptor (CD88) inhibition improves hypothermia-induced neuroprotection in an in vitro ischemic model.
AU - Thundyil, John
AU - Pavlovski, Dale
AU - Hsieh, Yu-Hsuan
AU - Gelderblom, Mathias
AU - Magnus, Tim
AU - Fairlie, David P
AU - Arumugam, Thiruma V
PY - 2012
Y1 - 2012
N2 - The concept of 'salvageble penumbra' has prompted both scientists and physicians to explore various neuroprotective approaches that could be beneficial during stroke therapy. Unfortunately, most of them have proved ineffective in targeting multiple cellular death cascades incited within the ischemic penumbra. Hypothermia has been shown to be capable of addressing this problem to some extent. Although many studies have shown that hypothermia targets several cellular processes, its effects on innate immune receptor-mediated apoptotic death still remain unclear. Moreover, whether inhibiting the signaling of innate immune receptors like complement anaphylatoxin C5a receptor (CD88) plays a role in this hypothermic neuroprotection still need to be deciphered. Using various types of ischemic insults in different neuronal cells, we confirm that hypothermia does indeed attenuate apoptotic neuronal cell death in vitro and this effect can be further enhanced by pharmacologically blocking or knocking out CD88. Thus, our study raises a promising therapeutic possibility of adding CD88 antagonists along with hypothermia to improve stroke outcomes.
AB - The concept of 'salvageble penumbra' has prompted both scientists and physicians to explore various neuroprotective approaches that could be beneficial during stroke therapy. Unfortunately, most of them have proved ineffective in targeting multiple cellular death cascades incited within the ischemic penumbra. Hypothermia has been shown to be capable of addressing this problem to some extent. Although many studies have shown that hypothermia targets several cellular processes, its effects on innate immune receptor-mediated apoptotic death still remain unclear. Moreover, whether inhibiting the signaling of innate immune receptors like complement anaphylatoxin C5a receptor (CD88) plays a role in this hypothermic neuroprotection still need to be deciphered. Using various types of ischemic insults in different neuronal cells, we confirm that hypothermia does indeed attenuate apoptotic neuronal cell death in vitro and this effect can be further enhanced by pharmacologically blocking or knocking out CD88. Thus, our study raises a promising therapeutic possibility of adding CD88 antagonists along with hypothermia to improve stroke outcomes.
KW - Animals
KW - Humans
KW - Treatment Outcome
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Cell Line
KW - Astrocytes/drug effects/physiology
KW - Brain Ischemia/drug therapy/therapy
KW - Hypothermia, Induced
KW - Neurons/drug effects/physiology
KW - Receptor, Anaphylatoxin C5a/antagonists & inhibitors
KW - Stroke/drug therapy/therapy
KW - Animals
KW - Humans
KW - Treatment Outcome
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Cell Line
KW - Astrocytes/drug effects/physiology
KW - Brain Ischemia/drug therapy/therapy
KW - Hypothermia, Induced
KW - Neurons/drug effects/physiology
KW - Receptor, Anaphylatoxin C5a/antagonists & inhibitors
KW - Stroke/drug therapy/therapy
M3 - SCORING: Journal article
VL - 14
SP - 30
EP - 39
JO - NEUROMOL MED
JF - NEUROMOL MED
SN - 1535-1084
IS - 1
M1 - 1
ER -
