Intranasal Administration of BDNF Improves Recovery and Promotes Neural Plasticity in a Neonatal Mouse Model of Hypoxic Ischemia.

IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Experimental Neurobiology Pub Date : 2024-02-29 DOI:10.5607/en23030
Serena-Kaye Sims, Madelynne Saddow, Lilly McGonegal, Catrina Sims-Robinson
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Abstract

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.

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鼻内注射 BDNF 可改善缺氧缺血新生小鼠模型的恢复并促进神经可塑性。
本研究探讨了鼻内注射脑源性神经营养因子(BDNF)对新生儿缺氧缺血(HI)模型中新生儿出生后第 7 天(P7)认知功能的益处。鼻内给药的吸引力在于它能促进 BDNF 在大脑和脊髓内的广泛分布。在这项研究中,我们评估了鼻内注射 BDNF 对改善 HI 后认知恢复的有效性。HI是通过结扎右颈动脉诱发的,随后在密闭室中暴露于8%的氧气/92%的氮气混合物中45分钟。作为护理标准,雌雄幼犬在温控室中接受 2 小时低体温。从HI后24小时开始,每天同一时间用Gilson移液管在清醒小鼠的每个鼻腔中注入生理盐水(对照组)或重组人BDNF(Harlan实验室)溶液,持续7天。我们使用新物体识别(NOR)和 Western 分析法评估了认知能力的恢复情况,以分析神经标记物和脑健康状况,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。我们的研究结果表明,在脑损伤后 24 小时内给予鼻内 BDNF 可改善脑损伤后 28 天和 42 天的物体辨别能力。我们的结果还表明,与注射生理盐水的 HI 动物相比,接受 BDNF 鼻内注射治疗的 HI 动物在第 42 天时突触素和 MAP2 均有所增加。
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来源期刊
Experimental Neurobiology
Experimental Neurobiology Neuroscience-Cellular and Molecular Neuroscience
CiteScore
4.30
自引率
4.20%
发文量
29
期刊介绍: Experimental Neurobiology is an international forum for interdisciplinary investigations of the nervous system. The journal aims to publish papers that present novel observations in all fields of neuroscience, encompassing cellular & molecular neuroscience, development/differentiation/plasticity, neurobiology of disease, systems/cognitive/behavioral neuroscience, drug development & industrial application, brain-machine interface, methodologies/tools, and clinical neuroscience. It should be of interest to a broad scientific audience working on the biochemical, molecular biological, cell biological, pharmacological, physiological, psychophysical, clinical, anatomical, cognitive, and biotechnological aspects of neuroscience. The journal publishes both original research articles and review articles. Experimental Neurobiology is an open access, peer-reviewed online journal. The journal is published jointly by The Korean Society for Brain and Neural Sciences & The Korean Society for Neurodegenerative Disease.
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