Abstract 1384: Impaired Neurogenesis in the Rostral Ventrolateral Medulla Cause Hypertension in Stroke-prone Spontaneously Hypertensive Rats
Background: Recent studies demonstrated that the neural progenitor cells that form neuroblasts were migrated directly to sites of brain injury in animal models of epilepsy, stroke, trauma, and neurodegenerative diseases. Moreover, apoptotic mechanisms are not just involved in apoptosis, but are also involved in the regulation of synaptic plasticity. It is not known, however, whether the balance between neuronal “birth” and “death” is impaired in the brain, particularly in the rostral ventrolateral medulla (RVLM), which determines sympathetic nerve activity. We examined the balance between neuroblasts, cell proliferation, and neural apoptosis in the RVLM of stroke-prone spontaneously hypertensive rats (SHRSP) in pre-hypertensive (6 – 8 weeks old) and hypertensive states (14 –16 weeks old).
Method and results: In SHRSP and age-matched Wistar-Kyoto (WKY) rats, we sampled the RVLM tissues by punched-out technique. We identified neuroblasts by staining for doublecortin (Dcx), cell proliferation by bromodeoxyuridine (BrdU), and neural apoptosis by staining for the active forms of caspase-3 and 9. In hypertensive states, SHRSP had significantly higher blood pressure than WKY, and significantly lower levels of Dcx and BrdU expression in the RVLM (evaluated by Western blot analysis) than WKY (Dcx;-43±4%, BrdU;-38±5%, n=5 for each, P<0.01). In pre-hypertensive states, the expressions of Dcx and BrdU in the RVLM were significantly decreased compared with WKY (Dcx;-33±5%, BrdU;-34±3%, n=4 for each, P<0.01), whereas blood pressure was similar between SHRSP and WKY. The expression levels of caspase-3 and 9 in the RVLM did not differ in SHRSP and WKY, in either pre-hypertensive or hypertensive states.
Conclusion: The impaired neurogenesis, identified by the migration of neuroblasts and neural proliferation, in the RVLM might be involved in hypertension in SHRSP.