Functional recovery from chronic spinal cord injury by the reactivation of endogenous microglia

FULL OPEN ONLINE ACCESS: Hamanoue, M. et al. Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells. Sci. Rep. 6, 24279; doi: 10.1038/srep24279 (2016).

During the chronic phase of spinal cord injury (SCI), fibrotic scar tissue was formed as if it was a barrier for regeneration. We hypothesized that reactivation of resting microglia, which are the resident macrophage in spinal cord, might eliminate such a structural barrier to prevent functional recovery. First, we investigated whether p38 MAP kinase (p38) could be an activator of residential microglia obtained from mice spinal cord. The addition of dominant active type of recombinant p38 protein (DA) to the culture medium promoted the activation of cultured microglia; the increased expression of growth factors including Glial cell-line derived neurotrophic factor, the phagocytotic clearance of spinal cord debris, and rapid phosphorylation of membrane protein obtained from the cultured microglia. In addition, continuous infusion of DA protein into the mice spinal cord for 7 days increased the number of Iba1-positive microglia. These results suggested that DA protein is an activator for microglia in the spinal cord. To ascertain the effect of DA protein on the chronic phase of SCI, DA injection into spinal cord was started three months after the contusion injury, and DA was injected intrathecally once a week for 2.5 months.

Society for Neuroscience Chicago 2015 Nanosymposium SCI: Therapeutic Strategies Trauma Presentation Number: 650.01
Support: KAKENHI 22500340 KAKENHI 24300197 the Strategic Research Foundation Grant-aided Project for Private Schools at Heisei 23rd from the Ministry of Education, Culture, Sports, Science and Technology of Japan, 2011–2015
Authors: *M. HAMANOUE1,2, K. MORIOKA3, K. HAYAKAWA4, K. NAKAJIMA5, T. OGATA6, K. TAKAMATSU1,2; 1Dept. of Physiol., Toho University Sch. of Med., Tokyo, Japan; 2Div. of Chronic Inflammatory Diseases, Advanced Med. Res. Ctr., Toho Univ. Grad. Sch. of Med., Tokyo, Japan; 3Neurolog. Surgery, Brain and Spinal Injury Ctr. (BASIC), San Francisco, CA; 4Orthopaedic Surgery, The Univ. of Tokyo, Grad. Sch. of Med., Tokyo, Japan; 5Sci. and Engin. for Sustainable Innovation, Fac. of Sci. and Engin., Soka Univ., Tokyo, Japan; 6Rehabil. for the Movement Functions, Natl. Rehabil. Ctr. for Persons with Disabilities, Saitama, Japan
Disclosures: M. Hamanoue: None. K. Morioka: None. K. Hayakawa: None. K. Nakajima: None. T. Ogata: None. K. Takamatsu: None.

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