Mey Jörg, J Morassutti Dante, Brook Gary, Liu Rong-Huan, Zhang Yi-Ping, Koopmans Guido, McCaffery Peter
Institute of Biology II, RWTH Aachen, Germany.
Eur J Neurosci. 2005 Mar;21(6):1555-68. doi: 10.1111/j.1460-9568.2005.03928.x.
Retinoic acid (RA) promotes growth and differentiation in many developing tissues but less is known about its influence on CNS regeneration. We investigated the possible involvement of RA in rat spinal cord injury (SCI) using the New York University (NYU) impactor to induce mild or moderate spinal cord contusion injury. Changes in RA at the lesion site were determined by measuring the activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at days 8-14 following the injuries. RALDH2 was the only detectable RALDH present in the control or injured spinal cord. The cellular localization of RALDH2 was identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected in oligodendroglia positive for the markers RIP and CNPase. Expression was also intense in the arachnoid membrane surrounding the spinal cord. After SCI the increase in RALDH2 was independent of the RIP- and CNPase-positive cells, which were severely depleted. Instead, RALDH2 was present in a cell type not previously identified as capable of synthesizing RA, that expressed NG2 and that was negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann cells and immature lymphocytes. We postulate that the RALDH2- and NG2-positive cells migrate into the injured sites from the adjacent arachnoid membrane, where the RALDH2-positive cells proliferate substantially following SCI. These findings indicate that close correlations exist between RA synthesis and SCI and that RA may play a role in the secondary events that follow acute SCI.
视黄酸（RA）在许多发育中的组织中促进生长和分化，但关于其对中枢神经系统再生的影响知之甚少。我们使用纽约大学（NYU）撞击器诱导大鼠脊髓轻度或中度挫伤性损伤，研究了RA在大鼠脊髓损伤（SCI）中的可能作用。通过测量其合成酶视网膜醛脱氢酶（RALDHs）的活性来确定损伤部位RA的变化。损伤后第4天酶活性显著增加，并在第8 - 14天达到峰值。RALDH2是对照或损伤脊髓中唯一可检测到的RALDH。通过免疫染色确定RALDH2的细胞定位。在未损伤的脊髓中，在对标记物RIP和CNPase呈阳性的少突胶质细胞中检测到RALDH2。在脊髓周围的蛛网膜中表达也很强烈。脊髓损伤后，RALDH2的增加与RIP和CNPase阳性细胞无关，这些细胞严重减少。相反，RALDH2存在于一种以前未被鉴定为能够合成RA的细胞类型中，该细胞表达NG2，并且对星形胶质细胞、少突胶质细胞、小胶质细胞、神经元、雪旺细胞和未成熟淋巴细胞的标记物呈阴性。我们推测RALDH2和NG2阳性细胞从相邻的蛛网膜迁移到损伤部位，在脊髓损伤后RALDH2阳性细胞在那里大量增殖。这些发现表明RA合成与脊髓损伤之间存在密切相关性，并且RA可能在急性脊髓损伤后的继发性事件中起作用。
