PMID- 12084437
OWN - NLM
STAT- MEDLINE
DCOM- 20020822
LR  - 20190724
IS  - 0022-510X (Print)
IS  - 0022-510X (Linking)
VI  - 199
IP  - 1-2
DP  - 2002 Jul 15
TI  - Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells 
      and improves functional outcome after MCAo in rats.
PG  - 17-24
AB  - Marrow stromal cells (MSCs) transplantation into brain has been employed to treat 
      experimental ischemia. However, MSCs undergo apoptosis and few survive in the 
      ischemic brain. We test the hypotheses that coadministration of bone marrow cells 
      (BMCs) with a cell-permeable inhibitor of caspases, 
      Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD), into the ischemic boundary zone 
      (IBZ) of brain promotes BMCs survival and improve outcome. Experimental groups 
      consist of: 24 h after MCAo, either phosphate-buffered saline (PBS, n=4), dead 
      BMC (n=4), fresh BMC (n=10), Z-VAD only (n=4), or BMC with Z-VAD (n=6) were 
      intracerebrally injected. BMCs were harvested from donor adult rats labeled with 
      bromodeoxyuridine (BrdU). Rats were subjected to an adhesive-removal 
      somatosensory and motor-rotarod functional tests before MCAo and at 1 and 7 days 
      after MCAo. Rats treated with a combination of Z-VAD and BMCs exhibited 
      significant improvement in the adhesive-removal test at 7 days compared with the 
      control group (combined MCAo+PBS and MCAo+dead BMC) (p<0.01), and the numbers of 
      BrdU-BMC increased (p<0.05) and apoptotic cells decreased (p<0.05) compared with 
      BMC alone transplantation. Our data suggest that intracerebral coadministration 
      of BMC with Z-VAD enhances the survival of grafted BMC and improves neurological 
      functional recovery after MCAo.
FAU - Chen, Jieli
AU  - Chen J
AD  - Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand 
      Boulevard, Detroit, MI 48202, USA.
FAU - Li, Yi
AU  - Li Y
FAU - Wang, Lei
AU  - Wang L
FAU - Lu, Mei
AU  - Lu M
FAU - Chopp, Michael
AU  - Chopp M
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Neurol Sci
JT  - Journal of the neurological sciences
JID - 0375403
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/*pharmacology
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - *Bone Marrow Transplantation
MH  - *Caspase Inhibitors
MH  - Cell Count
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Disease Models, Animal
MH  - Drug Administration Routes
MH  - Graft Survival/*drug effects
MH  - Infarction, Middle Cerebral Artery/*therapy
MH  - Male
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function
MH  - Stromal Cells/transplantation
MH  - Treatment Outcome
EDAT- 2002/06/27 10:00
MHDA- 2002/08/23 10:01
CRDT- 2002/06/27 10:00
PHST- 2002/06/27 10:00 [pubmed]
PHST- 2002/08/23 10:01 [medline]
PHST- 2002/06/27 10:00 [entrez]
AID - S0022510X02000758 [pii]
AID - 10.1016/s0022-510x(02)00075-8 [doi]
PST - ppublish
SO  - J Neurol Sci. 2002 Jul 15;199(1-2):17-24. doi: 10.1016/s0022-510x(02)00075-8.