Temporal variation of induction neurogenesis in a rat model of transient middle cerebral artery occlusion

Abstract

Objective: The adult brain is capable of neurogenesis after cerebral ischemia. We investigated the presence of new neural precursors after transient middle cerebral artery ischemia adult rats.Methods: Transient middle cerebral artery ischemia was induced in adult Wistar rats (n=13) using the monofilament method. In the experimental group (n=8), animals were harvested at days 3, 7, 10, 17 and 21 after ischemia. Five animals served as controls. Sagittal sections through the ischemic cortex were double-stained for neural (nestin and β-tubulin, nestin and PCNA), glial (nestin and GFAP) and oligodendroglial (nestin and O4, CNP and PCNA) precursors. Double-stained cells were also counted under high-power view and tabulated over time.Results: In the subventricular zone (SVZ), there was positive double-staining starting at day 3 showing proliferating astrocytic precursors (nestin + GFAP, 5–20% of cells), neuronal stem cells (nestin + PCNA, 95% of cells) and neuronal precursors (nestin + β-tubulin, 50% of cells). Within the penumbra, a more robust response showed more astrocytic precursors (50–80% of cells), premature and differentiated oligodendrocytes, neuronal stem cells (85% of cells) and neuronal precursors (15% of cells). In the area of the stroke, there was an intermediate response consisting of more astrocytic precursors (10–20% of cells), premature oligodendrocytes (45–100% of cells), neuronal stem cells (95% of cells) and neuronal precursors (25% of cells). Results were confirmed with cell counting analysis.Discussion: Our results show that not only do neural precursors proliferate in the SVZ, there is definite and real response in the penumbra and ischemic cortex, suggesting the ability of repair in the central nervous system.