Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage.
Previous studies show that intravascular injection of human bone marrow stromal cells (hBMSCs) significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we tested the hypothesis that mannitol improves the efficiency of intraarterial MSC delivery (i.e., fewer injected cells required for therapeutic efficacy) after ICH. There were four post-ICH groups (N=9): group 1, negative control with only intraarterial injection of 1 million human fibroblasts in phosphate-buffered saline (PBS); group 2, intravenous injection of mannitol alone in PBS (1.5 g/kg); group 3, intraarterial injection of 1 million hBMSCs alone in PBS; and group 4, intravenous injection of mannitol (1.5 g/kg) in PBS followed by intraarterial injection of 1 million hBMSCs in PBS. Group 4 exhibited significantly improved neurological functional outcome as assessed by neurological severity score (NSS) and corner test scores. Immunohistochemical staining of group 4 suggested increased synaptogenesis, proliferating immature neurons, and neuronal migration. The number of hBMSCs recruited to the injured region increased strikingly in group 4. Tissue loss was notably reduced in group 4. In summary, the beneficial effects of intraarterial infusion of MSCs are amplified with intravenous injection of mannitol. Preadministration of mannitol significantly increases the number of hBMSCs located in the ICH region, improves histochemical parameters of neural regeneration, and reduces the anatomical and pathological consequences of ICH.
Department of Neurosurgery, Henry Ford Health System, 2799 W Grand Boulevard, Detroit, MI 48202, USA. nsdos@neuro.hfh.edu
Donald M
DM
Seyfried
Yuxia
Y
Han
Dongmei
D
Yang
Jennifer
J
Ding
Smita
S
Savant-Bhonsale
Mohammad S
MS
Shukairy
Michael
M
Chopp
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000187:drug effects* / Q000502:physiology / Q000601:surgery; D020520:Brain Infarction / Q000503:physiopathology / Q000601:surgery / Q000628:therapy; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D004195:Disease Models, Animal; D004234:Diuretics, Osmotic / Q000494:pharmacology / Q000627:therapeutic use; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation; D006801:Humans; D008297:Male; D008353:Mannitol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation*; D016896:Treatment Outcome
D004234:Diuretics, Osmotic; D008353:Mannitol