title: FTY720 is neuroprotective and improves functional outcomes after intracerebral hemorrhage in mice.
abstract: 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.
authors: Department of Physiology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
authors: William B
authors: WB
authors: Rolland
authors: Anatol
authors: A
authors: Manaenko
authors: Tim
authors: T
authors: Lekic
authors: Yu
authors: Y
authors: Hasegawa
authors: Robert
authors: R
authors: Ostrowski
authors: Jiping
authors: J
authors: Tang
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D017364:Collagenases / Q000009:adverse effects; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D007839:Functional Laterality; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D009460:Neurologic Examination; D011409:Propylene Glycols / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000528:radiation effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D017364:Collagenases; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine