PMID- 10719070 OWN - NLM STAT- MEDLINE DCOM- 20000509 LR - 20190614 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 859 IP - 2 DP - 2000 Mar 24 TI - Infarct tolerance induced by intra-cerebral infusion of recombinant brain-derived neurotrophic factor. PG - 240-8 AB - Neuronal expression of brain-derived neurotrophic factor (BDNF) has been implicated in the mechanism of infarct tolerance (resistance to stroke) (H. Yanamoto et al., Infarct tolerance accompanied enhanced BDNF-like immunoreactivity in neuronal nuclei, submitted to Brain Res.), a process that takes more than 7 days following a preconditioning of repetitive cortical spreading depression (CSD). To investigate whether an elevated level of BDNF protein in the brain solely protects neurons against temporary focal ischemia, recombinant (r)BDNF was infused into the rat neocortex. Recombinant BDNF (or vehicle: saline) was administered into the left neocortex via an implanted osmotic minipump for 2.5, 7, 10 or 14 days pre-ischemia, during ischemia and for 2 days post-ischemia (8 microgram in total) in male Sprague-Dawley rats (n=6 each). Temporary focal ischemia was induced in the left middle cerebral artery (MCA) territory by three-vessel occlusion of bilateral common carotid arteries (CCAs) and MCA for 2 h, and the cerebral infarct volume was analyzed 2 days after ischemia using TTC staining. Regional cerebral blood flow (rCBF) of the left neocortex was monitored after 14 days of intracerebral administration of BDNF or vehicle (n=10 each). The distribution of BDNF following different periods of rBDNF or vehicle-infusion was analyzed using immunohistochemical techniques (n=5 each). In the groups treated with 8 microgram of rhBDNF for 7, 10, or 14 days pre-ischemia, there were significant reductions of neocortical infarct volume compared to in the control or vehicle-treated groups (p<0.05). In the rCBF study, there was no significant change after the infusion of 8 microgram rhBDNF for 14 days. In the histological study, a wide distribution of BDNF-like immunoreactivity in the neuronal nuclei in the ipsilateral neocortex was demonstrated after the infusion of 8 microgram rhBDNF for 14 days. The BDNF-like immunoreactivity in the neuronal nuclei was enhanced at the time that the resistance to stroke was achieved by direct intra-cerebral infusion of exogenous rBDNF. Elucidating the function of the BDNF-like protein located in the neuronal nuclei should reveal a new strategy for neuroprotection against ischemic brain attack in humans. FAU - Yanamoto, H AU - Yanamoto H AD - Laboratory for Cerebrovascular Disorders, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Japan. yanamoto@ri.ncvc.go.jp FAU - Nagata, I AU - Nagata I FAU - Sakata, M AU - Sakata M FAU - Zhang, Z AU - Zhang Z FAU - Tohnai, N AU - Tohnai N FAU - Sakai, H AU - Sakai H FAU - Kikuchi, H AU - Kikuchi H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Proteins) SB - IM MH - Animals MH - Blood Flow Velocity/physiology MH - Brain Ischemia/*drug therapy/*physiopathology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/metabolism/*pharmacology MH - Cerebral Cortex/*drug effects/pathology/*physiopathology MH - Cerebral Infarction/*drug therapy/*physiopathology MH - Cerebrovascular Circulation/physiology MH - Humans MH - Infusion Pumps MH - Male MH - Neurons/drug effects/pathology MH - Neuroprotective Agents/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Recombinant Proteins/*biosynthesis/*pharmacology MH - Reperfusion Injury/drug therapy/physiopathology MH - Time Factors EDAT- 2000/03/17 09:00 MHDA- 2000/05/16 09:00 CRDT- 2000/03/17 09:00 PHST- 2000/03/17 09:00 [pubmed] PHST- 2000/05/16 09:00 [medline] PHST- 2000/03/17 09:00 [entrez] AID - S0006-8993(00)01966-1 [pii] AID - 10.1016/s0006-8993(00)01966-1 [doi] PST - ppublish SO - Brain Res. 2000 Mar 24;859(2):240-8. doi: 10.1016/s0006-8993(00)01966-1.