Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury

• Published in: Experimental neurology Vol. 183; no. 2; pp. 406 - 417
• Main Authors: Rice, A.C, Khaldi, A, Harvey, H.B, Salman, N.J, White, F, Fillmore, H, Bullock, M.R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2003; Elsevier
• Subjects: Animals; Antigens, Differentiation - biosynthesis; Biological and medical sciences; Brain Injuries - pathology; Bromodeoxyuridine; Cell Differentiation; Cell Division; Confocal microscopy; Disease Models, Animal; Disease Progression; Flow cytometry; Injuries of the nervous system and the skull. Diseases due to physical agents; Lateral fluid percussion injury; Medical sciences; Mitosis; Neurogenesis; Neurons - pathology; Rats; Stem Cells - metabolism; Stem Cells - pathology; Traumas. Diseases due to physical agents; Lateral fluid percussion injury; Flow cytometry; Bromodeoxyuridine; Confocal microscopy; Neurogenesis; Human; Cell proliferation; Nervous system diseases; Brain stem; Stem cell; Tissue culture; Cell differentiation; Trauma; Cerebral disorder; Encephalon; Tubulin; Animal; Central nervous system disease; Progenitor cell
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00241-3

Recent studies have identified endogenous neural stem cells in adult rodent brains. The present study characterizes the early response of mitotically active cells in the brain to traumatic brain injury. Animals were subjected to lateral fluid percussion injury and sacrificed at various times after injury. To examine increases in cell proliferation animals were injected with the mitotic marker bromodeoxyuridine (BrdU) 24 h before sacrifice. Increased numbers of mitotically active cells were observed at 2 days in the subgranular zone (SGZ) and the subependymal zone (SEZ) under the injury site. To characterize the differentiation potential of these cells, animals were injected with BrdU 18 and 20 h after injury, then sacrificed at multiple time points after injury. Histologically, co-localization with βIII-tubulin (neuronal marker) and BrdU was evident at 10 and 15 days postinjury in the SGZ. Flow cytometry analysis was used to quantitatively assess neurogenesis in the SEZ. Animals were sacrificed 1, 5, or 10 days after injury and tissue sections extracted, grown in tissue culture for 24 h, fixed, and stained for nestin and βIII-tubulin to identify newly formed neurons. The percentage of cells expressing both markers was determined using flow cytometry analysis. There was a significant increase in newly differentiated neurons by 10 days postinjury in the SEZ. Thus, we conclude that traumatic brain injury stimulates an increase in proliferation of endogenous neural stem/progenitor cells and that a significant number of these express a neuronal marker. This response may be the brain’s way of trying to heal itself after injury.