Sims Serena-Kaye, Saddow Madelynne, McGonegal Lilly, Sims-Robinson Catrina
Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Biology, College of Charleston, Charleston, SC 29424, USA.
Exp Neurobiol. 2024 Feb 29;33(1):25-35. doi: 10.5607/en23030.
The benefit of intranasal brain derived neurotrophic factor (BDNF) treatment on cognitive function in a neonatal postnatal day 7 (P7) mouse model of hypoxic ischemia (HI) was explored. Intranasal delivery is attractive in that it can promote widespread distribution of BDNF within both the brain and spinal cord. In this study we evaluated the effectiveness of intranasal BDNF to improve cognitive recovery following HI. HI is induced via ligation of the right carotid artery followed by a 45-minute exposure to an 8% oxygen/ 92% nitrogen mixture in an enclosed chamber. Male and female pups were subjected to a 2-hour hypothermia in a temperature-controlled chamber as a standard of care. A solution of saline (control) or recombinant human BDNF (Harlan Laboratories) was administered with a Gilson pipette at the same time each day for 7 days into each nasal cavity in awake mice beginning 24 hours after HI. We evaluated cognitive recovery using the novel object recognition (NOR) and western analysis to analyze neuro-markers and brain health such as synaptophysin and microtubule associated protein -2 (MAP2). The objective of this study was to evaluate the role and therapeutic potential of BDNF in neonatal HI recovery. Our results indicate that intranasal BDNF delivered within 24 hours after HI improved object discrimination at both 28 and 42 days after HI. Our results also demonstrate increased synaptophysin and MAP2 at day 42 in HI animals that received intranasal BDNF treatment compared to HI animals that were administered saline.
探讨了鼻内给予脑源性神经营养因子（BDNF）对缺氧缺血（HI）新生7日龄（P7）小鼠模型认知功能的益处。鼻内给药具有吸引力，因为它可以促进BDNF在脑和脊髓中广泛分布。在本研究中，我们评估了鼻内给予BDNF改善HI后认知恢复的有效性。通过结扎右侧颈动脉，然后在封闭腔室中暴露于8%氧气/92%氮气混合物45分钟来诱导HI。作为标准护理，雄性和雌性幼崽在温度控制的腔室中进行2小时的低温治疗。从HI后24小时开始，每天在同一时间用吉尔森移液器将生理盐水（对照）或重组人BDNF（哈兰实验室）溶液给予清醒小鼠的每个鼻腔，持续7天。我们使用新颖物体识别（NOR）评估认知恢复，并通过蛋白质免疫印迹分析来分析神经标志物和脑健康，如突触素和微管相关蛋白-2（MAP2）。本研究的目的是评估BDNF在新生儿HI恢复中的作用和治疗潜力。我们的结果表明，HI后24小时内给予鼻内BDNF可改善HI后28天和42天的物体辨别能力。我们的结果还表明，与给予生理盐水的HI动物相比，接受鼻内BDNF治疗的HI动物在42天时突触素和MAP2增加。
