![]() We evaluated the effect of endogenously generated FGF-2 on neuronal regeneration, neuronal loss and GCL volume loss in the DG after TBI using mice genetically deficient in FGF-2. Cell loss in the GCL is assumed to contribute to the decrease in total volume of the GCL after injury ( 9). This model manifests progressive cell loss in the GCL as well as injured cortex ( 32– 35). In the present study, we used a controlled cortical impact (CCI) model of TBI to evaluate the contribution of FGF-2 to cell loss and cell addition in the granule cell layer (GCL) of DG after brain injury. The regulation and manipulation of neurogenesis and neurodegeneration via growth factor signaling has broad implications for both the development of therapeutic strategies for repair of CNS injury after trauma, and for advancing our understanding of basic cellular mechanisms of regeneration from brain injury. Recently, it was reported that intraventricular infusion of growth factors markedly augments endogenous progenitor proliferation, leading to regeneration of CA1 neurons and amelioration of neurologic deficits, after experimental cerebral ischemia ( 31). In addition, FGF-2 has been shown to reduce neuronal death after traumatic brain injury (TBI), cerebral ischemia, and seizures ( 27– 30). We have recently demonstrated that FGF-2 is critical for upregulation of neurogenesis in the adult DG after kainate-induced seizures and focal cerebral ischemia ( 15). ![]() ![]() FGF-2 and its family of receptors are widely distributed in the adult CNS ( 23– 25), and FGF-2 is released from cells in response to injury ( 26). Hippocampal neural progenitor cells in culture proliferate with only FGF-2 supplementation ( 17, 19, 20, 22). Among growth factors and neurotrophins that have been implicated, FGF-2 is regarded as one of the most potent ( 16– 21). However, what initiates and promotes this potentially therapeutic response in vivo is still unknown. For example, neural progenitor cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) can divide and differentiate into neurons after brain injury ( 8– 15). Neurogenesis in the mature nervous system is subject to physiologic and pathophysiologic regulation. However, this idea has been challenged by recent data showing that mammalian neural progenitor cells can proliferate and differentiate into neurons in the adult brain ( 1– 7). It has long been believed that the brain regenerates poorly after injury. These results suggest that FGF-2 upregulates neurogenesis and protects neurons against degeneration in the adult hippocampus after TBI, and that FGF-2 supplementation via gene transfer can reduce GCL degeneration after TBI. Furthermore, the decrease in GCL volume was also attenuated. Overexpression of FGF-2 by intracerebral injection of herpes simplex virus–1 amplicon vectors encoding this factor increased numbers of dividing cells (day 9) and BrdU-positive neurons (day 35) significantly in C57BL/6 mice. ![]() There was also a decrease in the volume of the GCL and the number of GCL neurons after TBI in both FGF-2 –/– and FGF-2 +/+ mice, but the decrease in both was greater in FGF-2 –/– mice at 35 days. However, in injured FGF-2 –/– mice, BrdU-positive cells and BrdU-positive neurons (days 9, 35) were fewer compared with FGF-2 +/+ mice. In both FGF-2 –/– and FGF-2 +/+ mice subjected to controlled cortical impact, the number of dividing cells labeled with BrdU, injected on posttrauma days 6 through 8, increased at 9 days after TBI, and the number of BrdU-positive cells colabeled with neuron-specific nuclear antigen significantly increased at 35 days. *Robert T.We studied the role of FGF-2 on regulation of neurogenesis and cell loss in the granule cell layer (GCL) of the hippocampal dentate gyrus after experimental traumatic brain injury (TBI). Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical-controlled, multicenter, double-blind study
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