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The Journal of Neuroscience, June 23, 2004, 24(25):5810-5815; doi:10.1523/JNEUROSCI.1109-04.2004

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Neurobiology of Disease
Stroke Transiently Increases Subventricular Zone Cell Division from Asymmetric to Symmetric and Increases Neuronal Differentiation in the Adult Rat

Ruilan Zhang,¹ Zhenggang Zhang,¹ Chunling Zhang,¹ Li Zhang,¹ Adam Robin,¹ Ying Wang,¹ Mei Lu,² and Michael Chopp^1,3

Departments of ¹Neurology and ²Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, and ³Department of Physics, Oakland University, Rochester, Michigan 48309

The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55% of dividing cells were oriented horizontally, whereas 40% were oriented vertically. Horizontal and vertical cleavage orientations produce asymmetric and symmetric divisions, respectively. Four days after stroke, the number of dividing cells increased twofold, whereas the proportion of symmetric dividing cells significantly (p < 0.01) increased from 40% before stroke to 60%. Fourteen days after stroke, the percentage of symmetric dividing cells was 47%. Stroke-increased numbers of dividing cells in M-phase were confirmed by immuostaining. In nonstroke rats, 37 and 33% of symmetric and asymmetric dividing cells, respectively, exhibited a neuronal marker (TuJ1). Four days after stroke, rats exhibited a significant (p < 0.05) augmentation of the frequency (47%) of neuronal distribution showing TuJ1 immunoreactivity in cells with symmetric division but not cells with asymmetric division (33%). Numb immunoreactivity was detected in SVZ cells of nonstroke rats. Stroke did not change Numb distribution. Our data suggest that neurons are produced by both asymmetric and symmetric cell divisions in the adult SVZ, and the transient increases in symmetric division and neuronal differentiation may result in stroke-induced neurogenesis.

Key words: focal cerebral ischemia; cell division; neural progenitor cells; subventricular zone; mitosis; rats

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Received Dec 22, 2003; revised May 12, 2004; accepted May 12, 2004.

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