TY - CHAP
T1 - FTY720 is Neuroprotective and Improves Functional Outcomes After Intracerebral Hemorrhage in Mice
AU - Rolland, William B.
AU - Manaenko, Anatol
AU - Lekic, Tim
AU - Hasegawa, Yu
AU - Ostrowski, Robert
AU - Tang, Jiping
AU - Zhang, John H.
N1 - Funding Information:
This study is partially supported by NIH NS053407 to J.H. Zhang and NS060936 to J. Tang.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Intracerebral hemorrhage (ICH) accounts for 20% of all strokes and is the most devastating form across all stroke types. Lymphocytes have been shown to potentiate cerebral inflammation and brain injury after stroke. FTY720 (Fingolimod) is an immune-modulating drug that prevents the egress of peripheral lymphocytes from peripheral stores. We hypothesized that FTY720 would reduce peripheral circulating lymphocytes, resulting in reduced brain injury and improved functional outcomes. CD-1 mice were anesthetized and then injected with collagenase into the right basal ganglia. Animals were divided into three groups: sham, ICH + Vehicle, and ICH + FTY720, by the intra-peritoneal route at 1 h after ICH induction. Brain water content was measured at 24 and 72 h. Neurobehavioral tests included corner test, forelimb use asymmetry, paw placement, wire-hang test, beam balance test, and a Neuroscore. FTY720 significantly reduced brain edema and improved neurological function at all time points tested. Lymphocyte modulation with FTY720 is an effective neuroprotective strategy to reduce brain injury and promote functional recovery after ICH. © 2011 Springer-Verlag/Wien.
AB - Intracerebral hemorrhage (ICH) accounts for 20% of all strokes and is the most devastating form across all stroke types. Lymphocytes have been shown to potentiate cerebral inflammation and brain injury after stroke. FTY720 (Fingolimod) is an immune-modulating drug that prevents the egress of peripheral lymphocytes from peripheral stores. We hypothesized that FTY720 would reduce peripheral circulating lymphocytes, resulting in reduced brain injury and improved functional outcomes. CD-1 mice were anesthetized and then injected with collagenase into the right basal ganglia. Animals were divided into three groups: sham, ICH + Vehicle, and ICH + FTY720, by the intra-peritoneal route at 1 h after ICH induction. Brain water content was measured at 24 and 72 h. Neurobehavioral tests included corner test, forelimb use asymmetry, paw placement, wire-hang test, beam balance test, and a Neuroscore. FTY720 significantly reduced brain edema and improved neurological function at all time points tested. Lymphocyte modulation with FTY720 is an effective neuroprotective strategy to reduce brain injury and promote functional recovery after ICH. © 2011 Springer-Verlag/Wien.
KW - Brain edema
KW - FTY720
KW - Fingolimod
KW - Intracerebral hemorrhage
KW - Lymphocytes
KW - Neurological function
KW - Neuroprotection
KW - Collagenases/adverse effects
KW - Cerebral Hemorrhage/chemically induced
KW - Fingolimod Hydrochloride
KW - Nervous System Diseases/etiology
KW - Functional Laterality
KW - Sphingosine/analogs & derivatives
KW - Brain Edema/etiology
KW - Animals
KW - Neurologic Examination
KW - Psychomotor Performance/radiation effects
KW - Analysis of Variance
KW - Time Factors
KW - Propylene Glycols/therapeutic use
KW - Immunosuppressive Agents/therapeutic use
KW - Mice
KW - Disease Models, Animal
UR - https://www.ncbi.nlm.nih.gov/pubmed/21725758
UR - https://www.mendeley.com/catalogue/0e783aa6-e185-386f-9710-68ff432536b8/
U2 - 10.1007/978-3-7091-0693-8_36
DO - 10.1007/978-3-7091-0693-8_36
M3 - Chapter (peer-reviewed)
C2 - 21725758
SN - 9783709106921
SN - 978-3-7091-2007-1
T3 - Acta Neurochirurgica, Supplementum
SP - 213
EP - 217
BT - Intracerebral Hemorrhage Research
PB - Springer Vienna
ER -