1. ¹Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA
2. ²Department of Physics, Oakland University, Rochester, Michigan, USA

Correspondence: Dr ZG Zhang, Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: zhazh@neuro.hfh.edu

Received 24 June 2008; Revised 20 August 2008; Accepted 9 September 2008; Published online 15 October 2008.

Abstract

Stroke increases neuroblasts in the subventricular zone (SVZ) of the lateral ventricle and these neuroblasts migrate toward the ischemic boundary to replace damaged neurons. Using brain slices from the nonischemic adult rat and transgenic mice that expressed enhanced green fluorescent protein (EGFP) concomitantly with doublecortin (DCX), a marker for migrating neuroblasts, we recorded electrophysiological characteristics while simultaneously analyzing the gene expression in single SVZ cells. We found that SVZ cells expressing the DCX gene from the nonischemic rat had a mean resting membrane potential (RMP) of -30 mV. DCX–EGFP-positive cells in the nonischemic SVZ of the transgenic mouse had a mean RMP of -257 mV and did not exhibit Na⁺ currents, characteristic of immature neurons. However, DCX–EGFP-positive cells in the ischemic SVZ exhibited a hyperpolarized mean RMP of -5418 mV and displayed Na⁺ currents, indicative of more mature neurons. Single-cell multiplex RT-PCR analysis revealed that DCX–EGFP-positive cells in the nonischemic SVZ of the transgenic mouse expressed high neural progenitor marker genes, Sox2 and nestin, but not mature neuronal marker genes. In contrast, DCX–EGFP-positive cells in the ischemic SVZ expressed tyrosine hydroxylase, a mature neuronal marker gene. Together, these data indicate that stroke changes gene profiles and the electrophysiology of migrating neuroblasts.