Disclosure of finding: This study was supported by Grant-in-aid from the Ministry of Education, Science and Culture of Japan (No.20591701, No.20390377, No.21390400, and No.23390342).
Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats
Article first published online: 12 JAN 2012
© 2012 Japanese Society of Neuropathology
Volume 32, Issue 5, pages 522–533, October 2012
How to Cite
Ito, M., Kuroda, S., Sugiyama, T., Maruichi, K., Kawabori, M., Nakayama, N., Houkin, K. and Iwasaki, Y. (2012), Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats. Neuropathology, 32: 522–533. doi: 10.1111/j.1440-1789.2011.01291.x
- Issue published online: 23 SEP 2012
- Article first published online: 12 JAN 2012
- Received 28 October 2011; revised and accepted 11 December 2011; published online 12 January 2012.
- bone marrow stromal cell;
- cell transplantation;
- neurovascular unit;
- neurovascular protection;
- stroke prone spontaneously hypertensive rat
This study was aimed to assess whether bone marrow stromal cells (BMSC) could ameliorate brain damage when transplanted into the brain of stroke-prone spontaneously hypertensive rats (SHR-SP). The BMSC or vehicle was stereotactically engrafted into the striatum of male SHR-SP at 8 weeks of age. Daily loading with 0.5% NaCl-containing water was started from 9 weeks. MRIs and histological analysis were performed at 11 and 12 weeks, respectively. Wistar-Kyoto rats were employed as the control. As a result, T2-weighted images demonstrated neither cerebral infarct nor intracerebral hemorrhage, but identified abnormal dilatation of the lateral ventricles in SHR-SP. HE staining demonstrated selective neuronal injury in their neocortices. Double fluorescence immunohistochemistry revealed that they had a decreased density of the collagen IV-positive microvessels and a decreased number of the microvessels with normal integrity between basement membrane and astrocyte end-feet. BMSC transplantation significantly ameliorated the ventricular dilatation and the breakdown of neurovascular integrity. These findings strongly suggest that long-lasting hypertension may primarily damage neurovascular integrity and neurons, leading to tissue atrophy and ventricular dilatation prior to the occurrence of cerebral stroke. The BMSC may ameliorate these damaging processes when directly transplanted into the brain, opening the possibility of prophylactic medicine to prevent microvascular and parenchymal-damaging processes in hypertensive patients at higher risk for cerebral stroke.