Neuroprotection and neurosupplementation in ischaemic brain.
Possible strategies for treating ischaemic stroke include: (i) neuroprotection (preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischaemia), and (ii) neurosupplementation (the repair of broken neuronal networks with newly born neurons in the chronic phase of cerebral ischaemia). In this paper, we review our recent progress in development of these distinct new strategies for treatment of damaged brain following a stroke. Firstly, we investigated the role of endogenous IL-6 (interleukin-6), which is one of the cytokines drastically induced by ischaemic stimuli, by administering IL-6RA (anti-IL-6 receptor monoclonal antibody) to mice. We found that endogenous IL-6 plays a critical role in neuroprotection and that its role may be mediated by STAT3 (signal transducer and activator of transcription-3) activation. Secondly, we studied the endogenous sources of the newly born neurons in the ischaemic striatum by region- and cell-type-specific cell labelling techniques. The results revealed that the SVZ (subventricular zone) is the principal source of the neuronal progenitors that migrate laterally towards the infarcted regions, and differentiate into newly born neurons. Finally, we developed a restorative stroke therapy with a bio-affinitive scaffold, which is an appropriate poly-porous structure releasing bioactive substances such as neurotrophic factor. This bio-affinitive scaffold is able to give an appropriate environment for newly born neurons. In future, we will combine these strategies to develop more effective therapies for treatment of strokes.
Yamashita
T
T
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Deguchi
K
K
Sawamoto
K
K
Okano
H
H
Kamiya
T
T
Abe
K
K
D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D020521:Stroke / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*
D018696:Neuroprotective Agents