Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Rutgers Biomedical & Health Sciences, MSB-H-512, 185 S. Orange Ave., Newark, NJ 07103, USA.
Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Rutgers Biomedical & Health Sciences, MSB-H-512, 185 S. Orange Ave., Newark, NJ 07103, USA.
Stem Cell Reports. 2017 Sep 12;9(3):972-984. doi: 10.1016/j.stemcr.2017.07.015. Epub 2017 Aug 17.
Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.
海马齿状回是创伤性脑损伤后神经发生和兴奋性增强的焦点。增加的神经发生被认为有助于受损网络的修复。我们的数据表明，在液压冲击性脑损伤后，神经发生的早期增加是短暂的，并且与年龄匹配的对照组相比，随后持续减少。神经发生的损伤后变化与神经前体细胞增殖的变化平行，并导致神经生成能力的长期下降。针对恢复损伤后神经发生至对照水平的靶向药理学逆转了神经生成能力的长期下降。限制损伤后神经发生减少了齿状回兴奋性和癫痫易感性的早期增加。我们的结果挑战了脑损伤后神经发生增加有益的假设，并表明损伤后早期神经发生的增加通过耗尽神经发生潜能和增强癫痫发生而对长期结果产生不利影响。旨在限制过度神经发生的治疗方法可能潜在地恢复神经增殖能力并限制脑损伤后的癫痫。
